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Auricular chondritis of unknown cause was suspected in a 10-year-old male Bolognese dog with a five-month history of painful bilateral nodular and ulcerative pyogranulomatous dermatitis of the pinnae with putative auricular cartilage destruction. Pain and lesions resolved with immunosuppressive doses of prednisolone, yet the condition resulted in deformity of both pinnae and external canals., (© 2024 ESVD and ACVD.)

Background: Numerous reports confirmed the safety and clinical efficacy of autologous adipose-derived stromal vascular fractions (SVF), which have recently been used to treat osteoarthritis (OA). However, there is still no consensus as to whether SVF can promote cartilage regeneration. Herein, the purpose of our study was to evaluate the effectiveness of SVF versus hyaluronic acid (HA) in cartilage regeneration by establishing a cartilage model based on the three-dimensional fat-suppressed spoiled gradient recalled echo (3D-FS-SPGR) sequence., Methods: Patients with symptomatic OA were recruited in our research, who were randomized into two groups. Meanwhile, patients in Kellgren-Lawrence (K-L) grades 2 and 3 were distinguished in each group. In the test group, patients received SVF injections of the knee, while patients in the control group received the same dose of HA. Each patient underwent the 3D-FS-SPGR sequence to establish a cartilage model at baseline, 6 months, and 12 months, respectively. The cartilage was characterized into six regions, and relevant parameters of the cartilage model were counted. Clinical and radiographic scores were recorded in one-year follow-up., Results: In all regions, the thickness and volume of cartilage defect and the volume of healthy cartilage were improved to some extent in the test group, especially the medial femoral condyle (MF) and medial tibial condyle (MT). In grades 2 and 3, the thickness and volume of cartilage defect decreased by 0.92 ± 0.18 mm and 1.03 ± 0.23 mm and 84.00 ± 32.30 mm 3 and 130.30 ± 49.56 mm 3 in MF and by 0.96 ± 0.22 mm and 0.99 ± 0.14 mm and 64.18 ± 21.40 mm 3 and 95.11 ± 19.93 mm 3 in MT, respectively. No such phenomenon was observed in the control group. Meanwhile, the SVF-treated knees showed significant improvement in clinical and radiographic scores at 12 months. Nevertheless, these scores of the control group became worse at 12-month follow-up visit., Conclusion: Taken together, this study shows that intra-articular injection of SVF markedly improved the clinical symptoms without adverse events, thereby repairing the damaged articular cartilage through cartilage regeneration., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Yin Zhang et al.)

Objective: Describe a series of cases of idiopathic chronic auricular chondritis refractory to antibiotics and steroids treated successfully with surgery., Study Design: Case series., Setting: Two tertiary academic medical centers., Patients: We analyzed four patients diagnosed with chronic auricular deformity, pain, and drainage for a period of 1 to 5 years who had failed prolonged treatment consisting of antibiotics, corticosteroids, and incision and drainage. All four patients were smokers, three were diabetic, and two had a history of bariatric surgery., Interventions: Operative subcutaneous partial auriculectomy (removal of diseased cartilage and excess skin) was performed., Main Outcome Measures: Resolution of pain and drainage, need for additional procedures, and reduction in narcotics required for pain control were analyzed., Results: Two of the four patients were given an immediate postoperative course of doxycycline and ciprofloxacin. With a minimum of 6 weeks' follow-up, all four patients had complete resolution of pain and recurrent drainage postoperatively. One patient requiring daily narcotic medication for pain and benzodiazepine for sleep preoperatively no longer required prescription medication. All specimens revealed chronic dermal and cartilage inflammation. Three of four cases had polymicrobial infection. One case had only skin contaminant growth on culture following multiple oral and parental antibiotic regimens., Conclusions: Surgical excision of diseased cartilage as a result of idiopathic chronic chondritis is an effective treatment in those cases refractory to antibiotics and incision and drainage, and should be considered in the treatment algorithm for similar patients, potentially offering definitive cure., Competing Interests: The authors disclose no funding and conflicts of interest., (Copyright © 2021, Otology & Neurotology, Inc.)

Objective: Collagen disruption is one of the underlying causes of knee pain in patients with osteoarthritis and/or diverse cartilage defects. Atelocollagen is a type of collagen that lacks telopeptides and thus has reduced antigenicity. The intra-articular injection of type I atelocollagen supplements collagen levels in the disrupted articular cartilage. This randomized controlled trial evaluated the effects of the intra-articular injection of atelocollagen for the management of knee pain., Design: Two hundred patients with osteoarthritis, chondromalacia, or other cartilage defects were randomly assigned to receive a 3-mL intra-articular injection of atelocollagen (BioCollagen group) or saline (Placebo group). Clinical improvement was evaluated over a 24-week period using the 100-mm visual analogue scale (VAS), the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and the 36-item Short-Form Health Survey (SF-36)., Results: VAS scores were significantly better in the BioCollagen group as compared with the Placebo group at 24 weeks. More patients in the BioCollagen group reported exceeding 20% and 40% VAS improvements. The WOMAC and SF-36 scores were also significantly improved from baseline after the intra-articular injection of atelocollagen; although, the differences between the BioCollagen and Placebo groups were not significant. There were no unexpected or severe adverse events reported for either group., Conclusions: The results show that an intra-articular injection of atelocollagen effectively alleviates knee pain, as intended. Therefore, the intra-articular injection of atelocollagen can be considered an alternative solution to controlling knee pain due to osteoarthritis and diverse cartilage defects.

Objective: Cartilage lesions in the knee joint can lead to joint mechanics changes and cause knee pain. Bone marrow stimulation (BMS) promotes cartilage regeneration by perforating the subchondral bone just below the injury and inducing bone marrow cells. This study aimed to investigate whether systemic administration of granulocyte colony-stimulating factor (G-CSF) with BMS improves repair of chronic partial-thickness cartilage defects (PTCDs)., Design: Eighteen 6-month-old New Zealand white rabbits were divided into 3 groups: control (C, n = 6), BMS alone ( n = 6), and BMS + G-CSF ( n = 6). Partial cartilage defects with 5 mm diameter were created in the trochlear region of both knees; after 4 weeks, the BMS alone and BMS + G-CSF groups underwent BMS; G-CSF (50 µg/kg) or saline was administered subcutaneously for 5 days starting from 3 days before BMS. At 8 and 16 weeks after cartilage defect creation, the area of cartilage defects was macroscopically and histologically evaluated., Results: International Cartilage Repair Society (ICRS) grades for macroscopic assessment were 0, 0.7, and 0.7 at 8 weeks and 0, 1.2, and 1.3 at 16 weeks in the C, BMS, and BMS + G-CSF groups, respectively. Wakitani scores for histological assessment were 9.8, 8.7, and 8.2 at 8 weeks and 9.5, 9, and 8.2 at 16 weeks in the C, BMS, and BMS + G-CSF groups, respectively. The BMS + G-CSF group showed significantly more repair than the C group, but there was no difference from the BMS group., Conclusions: The effect of BMS and G-CSF on chronic PTCDs in mature rabbit knees was limited.

Objective: The aim of this study is to evaluate the effects of intraarticular insulin on the treatment of chondral defects., Design: Twenty-four mature New Zealand rabbits were randomly divided into 3 groups as control (Group 1), microfracture (Group 2), and microfracture and insulin (Group 3). Four-millimeter full-thickness cartilage defects were created to the weight-bearing surface on the medial femoral condyles of each rabbit. In the first group, any additional interventions were not performed. Microfracture was performed on defects in groups 2 and 3. Additionally, 10 IU of insulin glargine was administrated into the knee joints of the third group. Three months after surgery, the knee joints were harvested and cartilage quality was assessed according to Wakitani and ICRS (International Cartilage Repair Society) scores histopathologically. Insulin injections were performed into the knees of 2 additional rabbits without creating a cartilage defect to evaluate the potential adverse effects of insulin on healthy cartilage (Group 4)., Results: The total ICRS and Wakitani scores of the insulin group were found to be significantly lower than the microfracture group but similar to the control group. No negative effects of insulin on healthy cartilage were detected. Intraarticular insulin after surgery has led to a statistically significant decrease in systemic blood sugar levels whereas the decrease observed after administration to intact tissues was not statistically significant., Conclusions: Insulin had a negative influence on the quality of cartilage regeneration and had no effect on healthy cartilage. Intraarticular insulin administration does not cause significant systemic effects in intact tissue.

Osteoarthritis (OA) is a common joint disease that is characterized by cartilage degradation. Iron deposition in the joints is common during the pathogenic progression of OA and recent studies have indicated that iron overload is an important contributor to OA progression. Calcium chelators have been reported to inhibit iron influx via modulating transferrin receptor protein 1 internalization, and they have been identified as a potential approach to the treatment of iron overload‑induced diseases. The aim of the present study was to investigate the effect of calcium chelators on the progression of iron overload‑induced OA. Primary chondrocytes were treated with various concentrations of ferric ammonium citrate (FAC) to mimic iron overload in vitro , followed by co‑treatment with the calcium chelator BAPTA acetoxymethyl ester (BAPTA‑AM). Subsequently, intracellular iron levels, cell viability, reactive oxygen species (ROS) levels, mitochondrial function and morphological changes, as well as MMP levels, were detected using commercial kits. It was demonstrated that FAC treatment significantly promoted chondrocyte apoptosis and the expression of MMPs, and these effects were reversed by co‑treatment with BAPTA‑AM. Moreover, BAPTA‑AM suppressed iron influx into chondrocytes and inhibited iron overload‑induced ROS production and mitochondrial dysfunction. These results indicated that calcium chelators may be of value in the treatment of iron metabolism‑related diseases and iron overload‑induced OA progression.

Objective: This study evaluated single intra-articular injections of Hymovis MO.RE., a hyaluronic acid hexadecyl derivative (HYADD4-G), to manage post-traumatic or degenerative knee or ankle chondropathy in professional soccer players., Patients and Methods: Twenty-five players affected by knee (n = 12) or ankle (n = 13) chondropathy were prospectively enrolled and treated by two single Hymovis MO.RE. (32 mg/4 ml) injections at the beginning of the football season (V0, baseline) and at mid-season (V1, 19-20 weeks thereafter), and were followed-up until the end of the season (V2, after further 19-20 weeks). Knee cases were evaluated using the 2000 IKDC knee subjective examination form and the modified Lysholm scoring system. Ankle cases were evaluated using the American Orthopaedic Foot Ankle Society (AOFAS) ankle-hindfoot score. Patients were also evaluated using a VAS Likert scale and a four-category scale recording both the patient's and the doctor's assessment on joint mobility in degrees and overall treatment efficacy. Adverse events, patient withdrawals and local reaction to injections were also assessed., Results: In knee patients, the 2000 IKDC subjective score improved from 46.8 ± 11.4 at V0 to 83.1 ± 12.5 at V2. Their modified Lysholm score improved from 58.8 ± 8.9 at V0 to 90.6 ± 8.3 at V2. In the ankle patients, the AOFAS score improved from 52.2 ± 5.6 at V0 to 96.4 ± 4.5 at V2. VAS Likert values and subjective evaluations improved at V1 and were maintained at V2. No side effects were recorded., Conclusions: A single Hymovis MO.RE. (32 mg/4 ml) intra-articular injection, repeated after 19-20 weeks, may be a viable option to improve symptoms and function in professional soccer players suffering from knee and ankle chondropathy.

Background: Atelocollagen is widely recognized as a biomaterial for regenerative medicine because of its good compatibility and low antigenicity. Injury of the outermost layer of articular cartilage, known as the lamina splendens, can lead to osteoarthritis (OA) and eventually full-thickness cartilage loss. The intra-articular injection of atelocollagen has been designed to restore the cartilage layer and cartilage defects in OA joints. In this study, we investigated the efficacy of atelocollagen as a cartilage supplement for joint defects., Methods: In this study, we evaluated the therapeutic effects of atelocollagen in animals with cartilage defects. Femoral groove defects were artificially created in 12 male New Zealand white rabbits, which were treated with intra-articular injection of either atelocollagen (experimental) or normal saline (control). The results were observed 3, 6, 9, and 12 weeks following macroscopic and histological evaluations., Results: At 3 weeks, cartilage tissue was restored in the experimental group, whereas the control group did not show signs of restoration. At 12 weeks, defects in both groups were filled with regenerated tissue, but the experimental group displayed a morphologically better appearance. Histologically, the regenerated tissue in the experimental group showed statistically significant improvement compared to the control group, with a structure similar to that of normal articular cartilage., Conclusion: The results showed that the intra-articular injection of atelocollagen enhanced cartilage regeneration following rabbit patellar groove defects. Therefore, intra-articular injection of atelocollagen can be used as an effective supplement for joint defects., (© 2021. The Korean Tissue Engineering and Regenerative Medicine Society.)

Background: Knee osteoarthritis is a common joint degenerative disease. Xiao Huoluo Pills (XHLP) has been used to treat degenerative diseases such as osteoarthritis and hyperosteogeny. However, XHLP's specific effective ingredients and mechanism of action against osteoarthritis have not been explored. Therefore, bioinformatics technology and molecular docking technology are employed in this study to explore the molecular basis and mechanism of XHLP in the treatment of knee osteoarthritis., Methods: Public databases (TCMSP, Batman-TCM, HERB, DrugBank, and UniProt) are used to find the effective active components and corresponding target proteins of XHLP (screening conditions: OB > 30%, DL ≥ 0.18). Differentially expressed genes related to cartilage lesions of knee osteoarthritis are obtained based on the GEO database (screening conditions: adjust P value < 0.01, |log 2 FC|≥1.0). The Venn package in R language and the BisoGenet plug-in in Cytoscape are adopted to predict the potential molecules of XHLP in the treatment of knee osteoarthritis. The XHLP-active component-target interaction network and the XHLP-knee osteoarthritis-target protein core network are constructed using Cytoscape software. Besides, GO/KEGG enrichment analysis on core genes is performed using the Bioconductor package and clusterProfiler package in the R language to explain the biological functions and signal pathways of the core proteins. Finally, molecular docking is performed through software such as Vina, LeDock, Discovery Studio 2016, PyMOL, AutoDockTools 1.5.6, so as to verify the binding ability between the active components of the drug and the core target protein., Results: XHLP has been screened out of 71 potentially effective active compounds for the treatment of OA, mainly including quercetin, Stigmasterol, beta-sitosterol, Izoteolin, and ellagic acid. Knee osteoarthritis cartilage lesion sequencing data (GSE114007) was screened out of 1672 differentially expressed genes, including 913 upregulated genes and 759 downregulated genes, displayed as heat maps and volcano maps. Besides, 33 core target proteins are calculated by Venn data package in R and BisoGenet plug-in in Cytoscape. The enrichment analysis on these target genes revealed that the core target genes are mainly involved in biological processes such as response to oxygen levels, mechanical stimulus, vitamin, drug, and regulation of smooth muscle cell proliferation. These core target genes are involved in signaling pathways related to cartilage degeneration of knee osteoarthritis such as TNF signaling pathway and PI3K-Akt signaling pathway. Finally, the molecular docking verification demonstrates that some active components of the drug have good molecular docking and binding ability with the core target protein, further confirming that XHLP has the effect of inhibiting cartilage degeneration in knee osteoarthritis., Conclusions: In this study, based on the research foundation of bioinformatics and molecular docking technology, the active components and core target molecules of XHLP for the treatment of cartilage degeneration of knee osteoarthritis are screened out, and the potential mechanism of XHLP inhibiting cartilage degeneration of knee osteoarthritis is deeply explored. The results provide theoretical basis and new treatment plan for XHLP in the treatment of knee osteoarthritis., (© 2021. The Author(s).)

Osteoarthritis (OA) is the most common articular degenerative disease characterized by chronic pain, joint inflammation, and movement limitations, which are significantly influenced by aberrant epigenetic modifications of numerous OA-susceptible genes. Recent studies revealed that both the abnormal activation and differential expression of histone deacetylases (HDACs) might contribute to OA pathogenesis. In this study, we investigated the chondroprotective effects of a marine-derived HDAC inhibitor, panobinostat, on anterior cruciate ligament transection (ACLT)-induced experimental OA rats. The intra-articular administration of 2 or 10 µg of panobinostat (each group, n = 7) per week from the 6th to 17th week attenuates ACLT-induced nociceptive behaviors, including secondary mechanical allodynia and weight-bearing distribution. Histopathological and microcomputed tomography analysis showed that panobinostat significantly prevents cartilage degeneration after ACLT. Moreover, intra-articular panobinostat exerts hypertrophic effects in the chondrocytes of articular cartilage by regulating the protein expressions of HDAC4, HDAC6, HDAC7, runt-domain transcription factor-2, and matrix metalloproteinase-13. The study indicated that HDACs might have different modulations on the chondrocyte phenotype in the early stages of OA development. These results provide new evidence that panobinostat may be a potential therapeutic drug for OA.

The hexosamine biosynthetic pathway (HBP) is essential for the production of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), the building block of glycosaminoglycans, thus playing a crucial role in cartilage anabolism. Although O-GlcNAcylation represents a protective regulatory mechanism in cellular processes, it has been associated with degenerative diseases, including osteoarthritis (OA). The present study focuses on HBP-related processes as potential therapeutic targets after cartilage trauma. Human cartilage explants were traumatized and treated with GlcNAc or glucosamine sulfate (GS); PUGNAc, an inhibitor of O-GlcNAcase; or azaserine (AZA), an inhibitor of GFAT-1. After 7 days, cell viability and gene expression analysis of anabolic and catabolic markers, as well as HBP-related enzymes, were performed. Moreover, expression of catabolic enzymes and type II collagen (COL2) biosynthesis were determined. Proteoglycan content was assessed after 14 days. Cartilage trauma led to a dysbalanced expression of different HBP-related enzymes, comparable to the situation in highly degenerated tissue. While GlcNAc and PUGNAc resulted in significant cell protection after trauma, only PUGNAc increased COL2 biosynthesis. Moreover, PUGNAc and both glucosamine derivatives had anti-catabolic effects. In contrast, AZA increased catabolic processes. Overall, "fueling" the HBP by means of glucosamine derivatives or inhibition of deglycosylation turned out as cells and chondroprotectives after cartilage trauma.

Introduction: Cannabinoids such as ▵-9-THC and CBD can downregulate the immune response by modulating the endocannabinoid system. This modulation is relevant for the treatment of prevalent autoimmune diseases (ADs), such as multiple sclerosis (MS), systemic lupus erythematosus (SLE), diabetes mellitus type 1 (DMT1), and rheumatoid arthritis (RA). These conditions require new therapeutic options with fewer side effects for the control of the autoimmune response. Objective: to conduct a literature review of preclinical scientific evidence that supports further clinical investigations for the use of cannabinoids (natural or synthetic) as potential immunomodulators of the immune response in ADs. Methodology: A systematic search was carried out in different databases using different MeSH terms, such as Cannabis sativa L., cannabinoids, immunomodulation, and ADs. Initially, 677 journal articles were found. After filtering by publication date (from 2000 to 2020 for SLE, DMT1, and RA; and 2010 to 2020 for MS) and removing the duplicate items, 200 articles were selected and analyzed by title and summary associated with the use of cannabinoids as immunomodulatory treatment for those diseases. Results: Evidence of the immunomodulatory effect of cannabinoids in the diseases previously mentioned, but SLE that did not meet the search criteria, was summarized from 24 journal articles. CBD was found to be one of the main modulators of the immune response. This molecule decreased the number of Th1 and Th17 proinflammatory cells and the production of the proinflammatory cytokines, interleukin (IL)-1, IL-12, IL-17, interferon (IFN)-γ, and tumor necrosis factor alpha, in mouse models of MS and DMT1. Additionally, new synthetic cannabinoid-like molecules, with agonist or antagonist activity on CB1, CB2, TRPV1, PPAR-α, and PPAR-γ receptors, have shown anti-inflammatory properties in MS, DMT1, and RA. Conclusion: Data from experimental animal models of AD showed that natural and synthetic cannabinoids downregulate inflammatory responses mediated by immune cells responsible for AD chronicity and progression. Although synthetic cannabinoid-like molecules were evaluated in just two clinical trials, they corroborated the potential use of cannabinoids to treat some ADs. Notwithstanding, new cannabinoid-based approaches are required to provide alternative treatments to patients affected by the large group of ADs.

Growth differentiation factor 5 (GDF-5) is essential for cartilage development and homeostasis. The expression and function of GDF-5 are highly associated with the pathogenesis of osteoarthritis (OA). OA, characterized by progressive degeneration of joint, particularly in cartilage, causes severe social burden. However, there is no effective approach to reverse the progression of this disease. Over the past decades, extensive studies have demonstrated the protective effects of GDF-5 against cartilage degeneration and defects. Here, we summarize the current literature describing the role of GDF-5 in development of cartilage and joints, and the association between the GDF-5 gene polymorphisms and OA susceptibility. We also shed light on the protective effects of GDF-5 against OA in terms of direct GDF-5 supplementation and modulation of the GDF-5-related signalling. Finally, we discuss the current limitations in the application of GDF-5 for the clinical treatment of OA. This review provides a comprehensive insight into the role of GDF-5 in cartilage and emphasizes GDF-5 as a potential therapeutic candidate in OA., (© 2021 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.)

Background: Chondrodermatitis nodularis helicis (CNH) is a common chronic condition characterized by a tender nodule on the helix or antihelix of the ear which may or may not have accompanying crusting, scaling, or ulceration and that is often difficult to treat., Objective: Develop an easy, effective, and durable treatment to reduce the pain and clinical signs including ulcerations associated with CNH using injectable hyaluronic acid (HA)., Materials and Methods: Twenty-four patients were injected and followed up in 2 to 4 weeks intervals using 0.2 to 0.3 mL of various HA with a high G-Prime., Results: Injectable HA significantly improved the symptoms and also the clinical appearance of all patients treated after 1 or 2 injections except 1 patient. Extrusion of the material through a preexisting ulcer usually required a second follow-up injection 2 weeks later. No adverse events were noted with the injections other than the intentional visible bulging of the injected region with HA., Conclusion: Injectable HA provides almost immediate relief from the discomfort of CNH in most cases in less than 1 or 2 weeks, significantly improves the clinical appearance over time and resolves accompanying ulcerations., (Copyright © 2020 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

The prevalence of osteoarthritis (OA) and the burden associated with the disease are steadily increasing worldwide, representing a major public health challenge for the coming decades. The lack of specific treatments for OA has led to it being recognized as a serious disease that has an unmet medical need. Advances in the understanding of OA pathophysiology have enabled the identification of a variety of potential therapeutic targets involved in the structural progression of OA, some of which are promising and under clinical investigation in randomized controlled trials. Emerging therapies include those targeting matrix-degrading proteases or senescent chondrocytes, promoting cartilage repair or limiting bone remodelling, local low-grade inflammation or Wnt signalling. In addition to these potentially disease-modifying OA drugs (DMOADs), several targets are being explored for the treatment of OA-related pain, such as nerve growth factor inhibitors. The results of these studies are expected to considerably reshape the landscape of OA management over the next few years. This Review describes the pathophysiological processes targeted by emerging therapies for OA, along with relevant clinical data and discussion of the main challenges for the further development of these therapies, to provide context for the latest advances in the field of pharmaceutical therapies for OA.

Background: The purpose of the study was to compare clinical and functional outcomes before and after hyaluronic acid (HA) injections in patients with osteochondral lesions of the talus who experienced a failure of their primary treatment with arthroscopic microfracture surgery., Methods: A total of 40 patients were included in the final study. These patients had received microfracture surgery but continued to experience postoperative pain over an average of 13.0 months (range, 0-81 months) and were available for investigation with a mean follow-up for 29.1 months (SD 14.7; range 2.6-79.6 months). All patients received intra-articular injections of HA once per week for 3 weeks. We assessed clinical and functional outcomes before and after injection using the American Orthopaedic Foot & Ankle Society (AOFAS) score, Foot and Ankle Outcome Score (FAOS), Short Form Health Survey (SF-36), the visual analog scale (VAS) for pain, and the Alexander subjective scale., Results: The AOFAS score significantly increased from 50.7 ± 13.8 to 79.9 ± 13.8 and the FAOS scores for symptom, pain, daily living, and sports were significantly higher postinjection compared to preinjection (all P < .001). Similarly, the mean VAS for pain was significantly decreased after 6 weeks following injection and continued to decrease over the follow-up period; the mean VAS was significantly lower postinjection compared to preinjection at 12 months ( P < .001)., Conclusion: Intra-articular HA injections on average significantly improved clinical and functional scores after failed primary operative treatment. HA injections may provide an alternative to secondary operative treatment and provide better clinical outcomes than other conservative treatments., Level of Evidence: Level II, prospective observational cohort study.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and progressive joint destruction. Chebulanin is a natural polyphenol acid isolated from the traditional Tibetan medicine Terminalia chebula Retz that has previously been reported to possess anti-inflammatory properties. The present study aimed to investigate the anti-inflammatory and anti-arthritic effects of chebulanin and explore its underlying mechanisms in vivo and in vitro using a collagen-induced arthritis (CIA) mouse model and lipopolysaccharide (LPS) stimulated RAW264.7 cell inflammation model. Arthritis severity scores were assessed twice weekly; the levels of cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum were detected using enzyme-linked immunosorbent assay kits; histopathological assessment was performed using micro computed tomography and hematoxylin and eosin staining. Activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were assessed using western blotting. The inhibition of translocation of cytosolic p38 and p65 into the nucleus was observed using immunofluorescence staining and western blotting in vitro. Chebulanin significantly suppressed the progression and development of RA in CIA mice by decreasing the arthritis severity scores, attenuating paw swelling and joint destruction, and reducing the levels of IL-6 and TNF-α significantly (p < 0.05). Furthermore, chebulanin reduced the levels of excised phosphorylated (p)-p38, phosphorylated-c-JUN N-terminal kinase (p-JNK), p-p65 and phosphorylated NF-κB inhibitor alpha (p-IκBα) in CIA mice, but did not affect the level of phosphorylated extracellular-signal-regulated kinase (ERK). In addition, chebulanin could inhibit the nuclear translocation of p38 and p65 in LPS-stimulated macrophages in dose-dependent manner. In conclusion, this study demonstrated that chebulanin exerts anti-inflammatory and anti-arthritic effects by inhibiting the activation of NF-κB and MAPK signaling pathways., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Objective: To describe the prevalence and antimicrobial susceptibility of bacterial isolates cultured from surgical specimens of infected arytenoid cartilage and granulomas., Study Design: Retrospective cohort study., Animals: Thirty-three thoroughbred horses., Methods: Hospital records were retrieved for all horses admitted to a referral hospital for arytenoid chondropathy surgery that had samples submitted for culture and sensitivity between 2005 and 2019. Descriptive analyses were performed., Results: In total, 56 bacterial isolates were obtained. Gram-positive bacteria (58%), Gram-negative bacteria (54%), and anaerobes (33%) were cultured from samples. Fifty-eight percent of horses had multiple bacteria isolated. Streptococcus spp were the most common (32%), followed by Enterobacteriaceae (13%). Bacterial isolates were sensitive to ceftiofur (83%), followed by ampicillin (64%), tetracycline (48%), enrofloxacin (45%), trimethoprim-sulfamethoxazole (41%), and gentamicin (18%). Multidrug resistance (MDR) was present in 44% of bacterial isolates., Conclusion: A wide variety of bacteria was cultured, providing evidence that secondary opportunistic infection by common respiratory bacteria is likely a factor in arytenoid chondropathy. Multidrug resistance was higher than what has been previously reported in equine respiratory samples. Trimethoprim-sulfamethoxazole had low effectiveness., Clinical Significance: Because culture and sensitivity testing is not available in the diagnosis of mild to moderate arytenoid chondropathy, the information from this study may allow for more targeted broad-spectrum antimicrobial treatment to limit disease progression when the disease is first identified. The antimicrobial susceptibilities and MDR found in this study emphasize the importance of following current antimicrobial guidelines and highlight the requirement for surgical intervention rather than continued medical treatment in cases that do not resolve with initial antimicrobial therapy., (© 2020 The American College of Veterinary Surgeons.)

Objective: To determine performance and repair kinetics of the ChonDux hydrogel scaffold for treating focal articular cartilage defects in the knee over 24 months., Design: This assessor-blinded trial evaluates ChonDux hydrogel scaffold implantation in combination with microfracture in 18 patients across 6 sites. Male and female patients 18 to 65 years of age with full-thickness femoral condyle defects 2 to 4 cm 2 in area were enrolled. Eligible patients received ChonDux treatment followed by rehabilitation. Defect volume fill was evaluated after 3, 6 (primary outcome), 12, 18, and 24 months by assessor blinded magnetic resonance imaging (MRI) analysis. Secondary outcomes were T2-weighted MRI relaxation time and patient surveys via visual analogue scale (VAS) pain and International Knee Documentation Committee (IKDC) knee function scoring., Results: ChonDux maintained durable tissue restoration over 24 months with final defect percent fill of 94.2% ± 16.3% and no significant loss of fill volume at any time points. Tissues treated with ChonDux maintained T2 relaxation times similar to uninjured cartilage between 12 and 24 months. VAS pain scoring decreased between 1 and 6 weeks, and IKDC knee function scores improved by approximately 30.1 with ChonDux over 24 months., Conclusion: ChonDux treatment is a safe adjunct to microfracture therapy and promotes stable restoration of full thickness articular cartilage defects for at least 24 months.

Rationale: Articular cartilage injury is quite common. However, post-injury cartilage repair is challenging and often requires medical intervention, which can be aided by 3D printed tissue engineering scaffolds. Specifically, the high accuracy of Melt Electro-Writing (MEW) technology facilitates the printing of scaffolds that imitate the structure and composition of natural cartilage to promote repair. Methods: MEW and Inkjet printing technology was employed to manufacture a composite scaffold that was then implanted into a cartilage injury site through microfracture surgery. While printing polycaprolactone (PCL) or PCL/hydroxyapatite (HA) scaffolds, cytokine-containing microspheres were sprayed alternately to form multiple layers containing transforming growth factor-β1 and bone morphogenetic protein-7 (surface layer), insulin-like growth factor-1 (middle layer), and HA (deep layer). Results: The composite biological scaffold was conducive to adhesion, proliferation, and differentiation of mesenchymal stem cells recruited from the bone marrow and blood. Meanwhile, the environmental differences between the scaffold's layers contributed to the regional heterogeneity of chondrocytes and secreted proteins to promote functional cartilage regeneration. The biological effect of the composite scaffold was validated both in vitro and in vivo . Conclusion: A cartilage repair scaffold was established with high precision as well as promising mechanical and biological properties. This scaffold can promote the repair of cartilage injury by using, and inducing the differentiation and expression of, autologous bone marrow mesenchymal stem cells., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Cartilage damage is still a threat to human beings, yet there is currently no treatment available to fully restore the function of cartilage. Recently, due to their unique structures and properties, injectable hydrogels have been widely studied and have exhibited high potential for applications in therapeutic areas, especially in cartilage repair. In this review, we briefly introduce the properties of cartilage, some articular cartilage injuries, and now available treatment strategies. Afterwards, we propose the functional and fundamental requirements of injectable hydrogels in cartilage tissue engineering, as well as the main advantages of injectable hydrogels as a therapy for cartilage damage, including strong plasticity and excellent biocompatibility. Moreover, we comprehensively summarize the polymers, cells, and bioactive molecules regularly used in the fabrication of injectable hydrogels, with two kinds of gelation, i.e., physical and chemical crosslinking, which ensure the excellent design of injectable hydrogels for cartilage repair. We also include novel hybrid injectable hydrogels combined with nanoparticles. Finally, we conclude with the advances of this clinical application and the challenges of injectable hydrogels used in cartilage repair., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Age-related bone deteriorations are the common endocrine disorders in the elderly population, leading to an increased risk of fractures. Therefore, effective treatment strategies provide a way to prevent bone loss and improve the quality of life in the elderly population. The present study aimed to investigate the anti-osteoporotic effects of doxercalciferol (DOX) in aging mice., Methods: Bone metabolism-related markers were measured by ELISA assay. The expression of bone formation and resorption-related genes was performed by RT-qPCR analysis. Hematoxylin and eosin (H&E) and Safranin O staining were performed to analyze the trabecular bone and cartilage degeneration., Results: Aging resulted in urine ca 2+ excretion, a decrease in bone ca 2+ content and reduction of biomechanical strength in mice. We also found that the level of PTH was increased in aging mice, while DOX administration markedly down-regulated serum PTH in aging mice. H&E and Safranin O staining showed that DOX protected against aging-induced bone loss and cartilage regeneration in the tibia from aging mice. Furthermore, DOX treatment resulted in an increase in Runx2, osterix and Col1a1 mRNA expression and a decrease in Ctsk, MMP-9 and CAII mRNA expression in the tibia from aging mice., Conclusion: These findings indicated that DOX had a beneficial effect on age-related bone deteriorations in aging mice by promoting osteoblast activity and cartilage regeneration and inhibiting osteoclast-specific genes expression., Competing Interests: No conflict of interest has been declared by the authors., (© Georg Thieme Verlag KG Stuttgart · New York.)

Osteoarthritis (OA) is a common degenerative disease that affects the musculoskeletal structure of the whole joint, which is characterized by progressive destruction of both articular cartilage and subchondral bone. Treatment of the bone pathologies, particularly osteoclast-mediated subchondral bone loss in the early stages of OA, could prevent subsequent cartilage degeneration and progression of OA. In the present study, the PKC inhibitor, Sotrastaurin, was found to inhibit RANKL-induced osteoclast formation in vitro in a dose- and time-dependent manner. In particular, SO exerted its anti-osteoclastic effect predominantly at the early stages of RANKL stimulation, suggesting inhibitory effects on precursor cell fusion. Using mature osteoclasts cultured on bovine bone discs, we showed that SO also exerts anti-resorptive effects on mature osteoclasts bone resorptive function. Mechanistically, SO attenuates the early activation of the p38, ERK and JNK signalling pathways, leeding to impaired induction of crucial osteoclast transcription factors c-Jun, c-Fos and NFATc1. We also showed that SO treatment significantly inhibited the phosphorylation of PKCδ and MARCKS, an upstream regulator of cathepsin K secretion. Finally, in animal studies, SO significantly alleviates the osteochondral pathologies of subchondral bone destruction as well as articular cartilage degeneration following DMM-induced OA, markedly improving OARSI scores. The reduced subchondral bone loss was associated with marked reductions in TRAP(+) osteoclasts in the subchondral bone tissue. Collectively, our data provide evidence for the protective effects of SO against OA by preventing aberrant subchondral bone and articular cartilage changes. Thus, SO demonstrates potential for further development as an alternative therapeutic option against OA., (© The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: The effects of tenascin-C (TNC) on cartilage repair were examined in cartilage defect model mice. An in vitro study was also performed to determine the mechanism of cartilage repair with TNC., Methods: Full-thickness osteochondral defects were filled with TNC (group A: 100 μg/ml, group B: 10 μg/ml, group C: empty). Mice were sacrificed at 1, 2, 3, and 6 weeks postoperatively. Cartilage repair was histologically evaluated using the modified WAKITANI score. Chondrocytes were isolated and cultured, and they were treated with TNC. The expressions of various mRNAs including TNC, inflammatory cytokines, and anabolic and catabolic factors for cartilage were compared by real-time polymerase chain reaction., Results: The defects in group A were covered with hyaline-like cartilage after 3 weeks. Average modified WAKITANI scores were significantly better in group A than in groups B and C at 3 and 6 weeks. TNC upregulated the expressions of endogenous TNC, inflammatory cytokines, and anabolic and catabolic factors for cartilage. TNC downregulated the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 5., Conclusions: Intra-articular injection of full-length TNC repaired cartilage in murine models of full-thickness osteochondral defects. TNC upregulated the expression of ADAMTS4, but downregulated the expression of ADAMTS5 that contributed to cartilage degradation., (Copyright © 2019 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Leonurine hydrochloride (LH) has been reported to exhibit a number of biological properties such as suppression of inflammation. This study aimed to examine whether the progression of osteoarthritis (OA) could be delayed by the administration of LH in an OA model. Rat chondrocytes were treated with LH under the condition of TNF-α-induced inflammation. After that, real-time PCR and Western blotting were conducted to evaluate relative gene/protein expression levels. For the in vivo study, rats were randomly allocated to a control group (anterior cruciate ligament transection (ACLT) surgery, treatment with saline) and LH group (ACLT surgery, treatment with LH). Articular cartilage degeneration was assessed by histological evaluation. It was found that LH significantly suppressed the expression of MMP-1, MMP-3, MMP-13, IL-6, and ADAMTS-5 in cells via the NF-κB signaling pathway. In addition, it is revealed that intra-articular injection of LH significantly ameliorated cartilage degeneration in a rat OA model. Taken together, these results indicate that LH attenuates progression of OA by inhibition of inflammation via the NF-κB signaling pathway and represents a potential preventive therapy for OA.

Introduction : The unique structure of bone and cartilage makes the systemic delivery of free drugs to those connective tissues very challenging. Consequently, effective and targeted delivery for bone and cartilage is of utmost importance. Engineered biodegradable polymers enable designing carriers for a targeted and temporal controlled release of one or more drugs in concentrations within the therapeutic range. Also, tissue engineering strategies can allow drug delivery to advantageously promote the in situ tissue repair. Areas covered : This review article highlights various drug delivery systems (DDS) based on biodegradable biomaterials to treat bone and/or cartilage diseases. We will review their applications in osteoporosis, inflammatory arthritis (namely osteoarthritis and rheumatoid arthritis), cancer and bone and cartilage tissue engineering. Expert opinion : The increased knowledge about biomaterials science and of the pathophysiology of diseases, biomarkers, and targets as well as the development of innovative tools has led to the design of high value-added DDS. However, some challenges persist and are mainly related to an appropriate residence time and a controlled and sustained release over a prolonged period of time of the therapeutic agents. Additionally, the poor prediction value of some preclinical animal models hinders the translation of many formulations into the clinical practice.

Background: Ageing-related failure of homeostasis mechanisms contributes to articular cartilage degeneration and osteoarthritis (OA), for which disease-modifying treatments are not available. Our objective was to identify molecules to prevent OA by regulating chondrocyte senescence and autophagy., Methods: Human chondrocytes with IL-6 induced senescence and autophagy suppression and SA-β-gal as a reporter of senescence and LC3 as reporter of autophagic flux were used to screen the Prestwick Chemical Library of approved drugs. Preclinical cellular, tissue and blood from OA and blood from OA and ageing models were used to test the efficacy and relevance of activating PPARα related to cartilage degeneration., Findings: Senotherapeutic molecules with pro-autophagic activity were identified. Fenofibrate (FN), a PPARα agonist used for dyslipidaemias in humans, reduced the number of senescent cells via apoptosis, increased autophagic flux, and protected against cartilage degradation. FN reduced both senescence and inflammation and increased autophagy in both ageing human and OA chondrocytes whereas PPARα knockdown conferred the opposite effect. Moreover, PPARα expression was reduced through both ageing and OA in mice and also in blood and cartilage from knees of OA patients. Remarkably, in a retrospective study, fibrate treatment improved OA clinical conditions in human patients from the Osteoarthritis Initiative (OAI) Cohort., Interpretation: These results demonstrate that FDA-approved fibrate drugs targeting lipid metabolism protect against cartilage degeneration seen with ageing and OA. Thus, these drugs could have immediate clinically utility for age-related cartilage degeneration and OA treatment. FUND: This study was supported by Instituto de Salud Carlos III- Ministerio de Ciencia, Innovación y Universidades, Spain, Plan Estatal 2013-2016 and Fondo Europeo de Desarrollo Regional (FEDER), "Una manera de hacer Europa", PI14/01324 and PI17/02059, by Innopharma Pharmacogenomics platform applied to the validation of targets and discovery of drugs candidates to preclinical phases, Ministerio de Economía y Competitividad, by grants of the National Instiutes of Health to PDR (P01 AG043376 and U19 AG056278). We thank FOREUM Foundation for Research in Rheumatology for their support., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: To determine if ipriflavone, a novel and safe inhibitor of Indian hedgehog (Ihh) signaling, can attenuate cartilage degeneration by blocking the Ihh pathway., Methods: Human chondrocytes were used to evaluate Ihh signaling, cell proliferation, apoptosis, gene, and protein expression of chondrocytes by cell proliferation and apoptosis assays, real-time qPCR, and Western blotting at 48 h after ipriflavone treatment. Human cartilage explants were further used to validate the cell culture results. The effects of ipriflavone on cartilage degeneration in vivo were assessed using the rat ACLT OA model. Two-month-old male SD rats were randomized into 3 groups (n = 75): (1) sham, (2) ACLT alone, and (3) ACLT+ ipriflavone. Ipriflavone was administered intragastrically at 24 h after ACLT for 6 weeks. The extent of OA progression was evaluated by the OARSI score and immunohistochemistry at 12 weeks after surgery. The Ihh signaling pathway and OA-related genes were quantified by real-time PCR., Results: Cell proliferation in the cells treated with ipriflavone was increased to 36.40% ± 1.32% (5 μM) and 28.54% ± 0.74% (10 μM) from 11.99% ± 0.35% (DMSO) (P < 0.001), and apoptosis was decreased to 12.64% ± 3.7% (5 μM) and 15.18% ± 3.13% (10 μM) from 25.76% ± 5.1% (DMSO) (P < 0.05). Ipriflavone blocked Runx-2 mainly through the Smo-Gli2 pathway. A similar result was found in the cartilage explant culture. Ihh signaling in vivo was inhibited in animals treated with ipriflavone. Safranin-O staining revealed a less cartilage damage with lower OARSI scores (P < 0.05) in the ipriflavone-treated animals compared with untreated animals. The gene expression of Smo and Gli2 was inhibited significantly by ipriflavone (P < 0.05). The OA-related gene and protein type X, MMP-13, and type II collagen-C fragment were reduced, while type II collagen and Agg were increased in the ipriflavone-treated animals (P < 0.05)., Conclusions: Catabolic genes were disrupted by blocking the Ihh pathway. This finding suggests that disruption of Ihh signaling with ipriflavone provides chondral protection in rat posttraumatic OA.

Osteoarticular infections include septic arthritis and osteomyelitis, with Gram-positive microorganisms isolated most frequently. In recent years, there has been an increase in the number of resistant strains in this type of infection, which complicates the treatment. Fosfomycin is active against a large percentage of Gram-positive and Gram-negative pathogens, including multidrug-resistant strains, and its properties include low protein binding, low molecular weight and good bone dissemination. In this article, we discuss fosfomycin's activity in vitro, its pharmacokinetic and pharmacodynamic parameters of interest in osteoarticular infections, the experimental models of osteomyelitis and foreign body infection and the clinical experience with these types of infections.

The aim of the present study was to investigate the effects of phosphorylatable nucleus localization signal linked nucleic kinase substrate short peptide ( p NNS)-conjugated chitosan ( p NNS-CS) mediated miR-140 and IGF-1 in both rabbit chondrocytes and cartilage defects model. p NNS-CS was combined with pBudCE4.1-IGF-1, pBudCE4.1-miR-140, and negative control pBudCE4.1 to form pDNA/ p NNS-CS complexes. Then these complexes were transfected into chondrocytes or injected intra-articularly into the knee joints. High levels of IGF-1 and miR-140 expression were detected both in vitro and in vivo . Compared with pBudCE4.1 group, in vitro , the transgenic groups significantly promoted chondrocyte proliferation, increased glycosaminoglycan (GAG) synthesis, and ACAN, COL2A1, and TIMP-1 levels, and reduced the levels of nitric oxide (NO), MMP-13, and ADAMTS-5. In vivo , the exogenous genes enhanced COL2A1, ACAN, and TIMP-1 expression in cartilage and reduced cartilage Mankin score and the contents of NO, IL-1 β , TNF- α , and GAG contents in synovial fluid of rabbits, MMP-13, ADAMTS-5, COL1A2, and COL10A1 levels in cartilage. Double gene combination showed better results than single gene. This study indicate that p NNS-CS is a better gene delivery vehicle in gene therapy for cartilage defects and that miR-140 combination IGF-1 transfection has better biologic effects on cartilage defects.

Articular cartilage defects are prevalent and are potentially involved in the initiation of osteoarthritis, yet the lack of efficient therapeutic options to treat cartilage defects represents a substantial challenge. Molecular treatments that require the delivery of therapeutic gene vectors are often less effective that specific, targeted approaches, and the scientific evidence for acellular biomaterial-assisted procedures is limited. Controlled delivery of gene vectors using biocompatible materials is emerging as a novel strategy for the sustained and tuneable release of gene therapies in a spatiotemporally precise manner, thereby reducing intra-articular vector spread and possible loss of the therapeutic gene product. Controlled, biomaterial-guided delivery of gene vectors could be used to enhance intrinsic mechanisms of cartilage repair while affording protection against potentially damaging host immune responses that might counteract the gene therapy component. This Review provides an overview of advances in gene vector-loaded biomaterials for articular cartilage repair. Such systems enable the sustained release of gene therapies while maintaining transduction efficacy. Strategies that harness these properties are likely to result in improved in situ cartilage tissue regeneration that could be safely translated into clinical applications in the near future.

Notoginseng Radix and Rehmanniae Radix Preparata have been widely used traditionally for treating inflammatory diseases. This research studies the therapeutic effects of YH23537, the extracts of Notoginseng Radix and Rehmanniae Radix Preparata, on pain and cartilage degeneration in an experimental osteoarthritis (OA) model. Male Wistar rats were inoculated intra-articularly with 3 mg of monosodium iodoacetate (MIA) in the right intra-articular. Four days later, the animals were administrated orally with YH23537 daily for 24 days. Tactile allodynia and weight bearing were measured. Macroscopic and microscopic observations for articular cartilage were performed at the end of the experiment. Protein expression in the joint was determined by immunohistochemistry. The effects of YH23537 on mRNA levels in chondrocytes stimulated with interleukin (IL)-1β were analyzed using random polymerase chain reaction. OA induction was confirmed by significant decrease of paw withdrawal latency, paw withdrawal threshold, and weight bearing compared with the normal group at 3 days after MIA injection. The YH23537-treated groups displayed significant increases in pain thresholds and weight bearing throughout the observation period. The damage to articular cartilage was significantly lessened visually and histopathologically by YH23537 treatment. YH23537 suppressed the expression of metalloproteinase-3, nitrotyrosine, IL-1β and IL-6 increased in OA joints. YH23537 upregulated tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-3 in IL-1β-stimulated human OA chondrocytes. The protein levels of the NF-κBp65 and HIF-2α in the joint tissues were reduced by YH23537. YH23537 exerted antinociceptive effects and cartilage protective effects in experimental OA rats by suppressing oxidative injury, inflammatory mediators, and inducing anabolic factors. We suggest that YH23537 may have efficacy for treating OA in humans.

Objectives During arthroscopic or open joint surgery, articular cartilage may be subjected to mechanical insults by accident or design. These may lead to chondrocyte death, cartilage breakdown and posttraumatic osteoarthritis. We have shown that increasing osmolarity of routinely used normal saline protected chondrocytes against injuries that may occur during orthopedic surgery. Often several liters of irrigation fluid are used during an orthopedic procedure, which is usually kept at room temperature, but is sometimes chilled. Here, we compared the effect of normal and hyperosmolar saline solution at different temperatures on chondrocyte viability following cartilage injury using in vitro and in vivo models of scalpel-induced injury. Design Cartilage injury was induced in bovine osteochondral explants and the patellar groove of rats in vivo by a single pass of a scalpel blade in the presence of normal saline (300 mOsm) or hyperosmolar saline solution (600 mOsm, sucrose addition) at 4°C, 21°C, or 37°C. Chondrocytes were fluorescently labeled and visualized by confocal microscopy to assess cell death. Results Hyperosmolar saline reduced scalpel-induced chondrocyte death in both bovine and rat cartilage by ~50% at all temperatures studied (4°C, 21°C, 37°C; P < 0.05). Raising temperature of both irrigation solutions to 37°C reduced scalpel-induced cell death ( P < 0.05). Conclusions Increasing the osmolarity of normal saline and raising the temperature of the irrigation solutions to 37°C reduced chondrocyte death associated with scalpel-induced injury in both in vitro and in vivo cartilage injury models. A hyperosmolar saline irrigation solution at 37°C may protect cartilage by decreasing the risk of chondrocyte death during mechanical injury.

Background: Osteoarthritis (OA) is one of the complex diseases that affect a large population of the world. The aim of the current study was to explore the roles of taurine in OA rat models, and discover the related mechanisms., Methods: OA rat models were established by anterior cruciate ligament transection (ACLT) plus medial meniscus resection (MMx) surgery on the right knees. Secondary mechanical allodynia, weight-bearing alterations and knee joint width were evaluated before surgery and every two weeks after surgery. At 14weeks, histopathological analysis was conducted on the knee joint cartilage. Protein amount of MMP-3 and CHOP was evaluated by western blot., Results: Taurine injection after surgery significantly relieved the symptoms of OA in rat models in a dose-dependent and time-dependent manner, as shown by alleviation of secondary mechanical allodynia, decrease in hind limb weight-bearing alterations, and inhibited knee swelling. Moreover, histopathological analysis showed that taurine inhibited matrix loss and cartilage degeneration in a dose-dependent manner. Taurine administration strikingly suppressed the expression of matrix metalloproteinase-3 (MMP-3) and CHOP., Conclusion: These results indicated that taurine administration exhibited protective effects by inhibiting MMP-3 and CHOP expression, and subsequently alleviated the OA symptoms in experimental rat models., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Human adult articular cartilage (AC) has little capacity for repair, and joint surface injuries often result in osteoarthritis (OA), characterised by loss of matrix, hypertrophy and chondrocyte apoptosis. Inflammation mediated by interleukin (IL)-6 family cytokines has been identified as a critical driver of proarthritic changes in mouse and human joints, resulting in a feed-forward process driving expression of matrix degrading enzymes and IL-6 itself. Here we show that signalling through glycoprotein 130 (gp130), the common receptor for IL-6 family cytokines, can have both context-specific and cytokine-specific effects on articular chondrocytes and that a small molecule gp130 modulator can bias signalling towards anti-inflammatory and antidegenerative outputs., Methods: High throughput screening of 170 000 compounds identified a small molecule gp130 modulator termed regulator of cartilage growth and differentiation (RCGD 423) that promotes atypical homodimeric signalling in the absence of cytokine ligands, driving transient increases in MYC and pSTAT3 while suppressing oncostatin M- and IL-6-mediated activation of ERK and NF-κB via direct competition for gp130 occupancy., Results: This small molecule increased proliferation while reducing apoptosis and hypertrophic responses in adult chondrocytes in vitro. In a rat partial meniscectomy model, RCGD 423 greatly reduced chondrocyte hypertrophy, loss and degeneration while increasing chondrocyte proliferation beyond that observed in response to injury. Moreover, RCGD 423 improved cartilage healing in a rat full-thickness osteochondral defect model, increasing proliferation of mesenchymal cells in the defect and also inhibiting breakdown of cartilage matrix in de novo generated cartilage., Conclusion: These results identify a novel strategy for AC remediation via small molecule-mediated modulation of gp130 signalling., Competing Interests: Competing interests: DE, BVH and VJ are inventors onPCT/US16/20126. DE and BVH are cofounders and shareholdersof CarthroniX., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective To critically evaluate the current basic science, translational, and clinical data regarding bone marrow aspirate concentrate (BMAC) in the setting of focal cartilage defects of the knee and describe clinical indications and future research questions surrounding the clinical utility of BMAC for treatment of these lesions. Design A literature search was performed using the PubMed and Ovid MEDLINE databases for studies in English (1980-2017) using keywords, including ["bone marrow aspirate" and "cartilage"], ["mesenchymal stem cells" and "cartilage"], and ["bone marrow aspirate" and "mesenchymal stem cells" and "orthopedics"]. A total of 1832 articles were reviewed by 2 independent authors and additional literature found through scanning references of cited articles. Results BMAC has demonstrated promising results in the clinical application for repair of chondral defects as an adjuvant procedure or as an independent management technique. A subcomponent of BMAC, bone marrow derived-mesenchymal stem cells (MSCs) possess the ability to differentiate into cells important for osteogenesis and chondrogenesis. Modulation of paracrine signaling is perhaps the most important function of BM-MSCs in this setting. In an effort to increase the cellular yield, authors have shown the ability to expand BM-MSCs in culture while maintaining phenotype. Conclusions Translational studies have demonstrated good clinical efficacy of BMAC both concomitant with cartilage restoration procedures, at defined time points after surgery, and as isolated injections. Early clinical data suggests BMAC may help stimulate a more robust hyaline cartilage repair tissue response. Numerous questions remain regarding BMAC usage, including cell source, cell expansion, optimal pathology, and injection timing and quantity.

Objective Focal chondral defects alter joint mechanics and cause pain and debilitation. Microfracture is a surgical technique used to treat such defects. This technique involves penetration of subchondral bone to release progenitor cells and growth factors from the marrow to promote cartilage regeneration. Often this results in fibrocartilage formation rather than structured hyaline cartilage. Some reports have suggested use of growth hormone (GH) with microfracture to augment cartilage regeneration. Our objective was to test whether intra-articular (IA) GH in conjunction with microfracture, improves cartilage repair in a rabbit chondral defect model. We hypothesized that GH would exhibit a dose-dependent improvement in regeneration. Design Sixteen New Zealand white rabbits received bilateral femoral chondral defects and standardized microfracture repair. One group of animals ( n = 8) received low-dose GH by IA injection in the left knee, and the other group ( n = 8) received high-dose GH in the same manner. All animals received IA injection of saline in the contralateral knee as control. Serum assays, macroscopic grading, and histological analyses were used to assess any improvements in cartilage repair. Results Peripheral serum GH was not elevated postoperatively ( P = 0.21). There was no improvement in macroscopic grading scores among either of the GH dosages ( P = 0.83). Scoring of safranin-O-stained sections showed no improvement in cartilage regeneration and some evidence of increased bone formation in the GH-treated knees. Conclusions Treatment with either low- or high-dose IA GH does not appear to enhance short-term repair in a rabbit chondral defect model.

Objective: To study the effect of Bushen Huoxue decoction on calcification of cartilage endplate in lumbar vertebrae., Methods: Six healthy male gerbils with 2-month-old were selected as normal control group, and 24 7-month-old healthy male gerbils were fed to 12-month-old to establish the aged gerbil model. Thirty gerbils were randomly divided into five groups as follow: the normal control group ( n =6), model group ( n =6, normal saline 4 ml/kg, intragastric 30 d), Bushen Huoxue low dose group( n =6, 1.9× 10⁻ ³ ml/g given Bushen Huoxue recipe orally, 30 d), Bushen Huoxue middle dose group( n =6, 3.8× 10⁻ ³ ml/g given Bushen Huoxue recipe orally, 30 d), Bushen Huoxue high dose group( n =6, 7.6× 10⁻ ³ ml/g given Bushen Huoxue recipe orally, 30 d), the intervention group administered for 1.36 g from 7-month-old age, 30 d. The animals were sacrificed at the age of 2 months in the normal control group and 12 months of age in the other groups. The morphology of the lumbar vertebral cartilage endplate, the area of vascular bud, the ratio of non-calcified/calcified layer were analysis by HE chromosome visual method. The expression of type X collagen and BMPs in cartilage endplates were detected by rabbit monoclonal immunohistochemical staining., Results: The relative area of the vascular buds cartilage endplate measurements showed that compared with the model group, middle dose group and normal control group increased ( P <0.05), high and low dose groups all had different degrees of increase, but no statistical significance( P >0.05). The ratio of cartilage endplate thickness of non-calcified/calcified showed that compared with the model group, Bushen Huoxue middle dose, normal control group increased, with statistical significance( P <0.05), and high and low dose groups all had different degrees of increase, but there were no statistical significance( P >0.05). Compared with the model group, the expression of type X collagen in the cartilage endplate of the normal group, the Bushen Huoxue low, middle and high dose groups decreased, and had statistical significance( P <0.01); compared with the model group, the expression of BMPs in the normal group, Bushen Huoxue middle dose group increased, with statistically significant( P <0.01), while the high and low dose groups increased in different degrees, but there was no statistical significance( P >0.05)., Conclusions: Bushen Huoxue prescription can delay the calcification of cartilage endplate in the process of aging, suggesting that it can be used as a preventive medicine for early disc degeneration., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

Purpose of Review: We give an update on the etiology and potential treatment options of rare inherited monogenic disorders associated with arterial calcification and calcific cardiac valve disease., Recent Findings: Genetic studies of rare inherited syndromes have identified key regulators of ectopic calcification. Based on the pathogenic principles causing the diseases, these can be classified into three groups: (1) disorders of an increased extracellular inorganic phosphate/inorganic pyrophosphate ratio (generalized arterial calcification of infancy, pseudoxanthoma elasticum, arterial calcification and distal joint calcification, progeria, idiopathic basal ganglia calcification, and hyperphosphatemic familial tumoral calcinosis; (2) interferonopathies (Singleton-Merten syndrome); and (3) others, including Keutel syndrome and Gaucher disease type IIIC. Although some of the identified causative mechanisms are not easy to target for treatment, it has become clear that a disturbed serum phosphate/pyrophosphate ratio is a major force triggering arterial and cardiac valve calcification. Further studies will focus on targeting the phosphate/pyrophosphate ratio to effectively prevent and treat these calcific disease phenotypes.

Background: Therapies used to treat chondrodermatitis nodularis helicis (CNH), such as surgical excision, pressure relief, or topical steroids report varying degrees of success., Objective: We evaluated the response and safety of methyl aminolevulinate (MAL) photodynamic therapy (PDT) in CNH., Methods: This retrospective, observational study performed at the University Hospital Ramon y Cajal (Madrid, Spain) and Hospital San Jorge (Huesca, Spain) included all patients diagnosed with CNH and treated with MAL-PDT from 2008 to 2015. Treatment sites were prepared and irradiated as per the conventional MAL-PDT procedure., Results: Patients underwent a mean of 2.3 sessions with between-session intervals ranging from 15 days to 1 month. A complete response to PDT was observed in 33 patients (76.7%), who experienced pain relief and resolution of the inflammatory nodule. Lesion recurrence was recorded in 10 patients (23.3%) during the mean follow-up period of 20 months. Receiving ≥2 PDT sessions was significantly associated with a good response (26/28, 93% success rate, P = .003)., Limitations: Some limitations of the study are the lack of an established between-session interval, the absence of evaluation of curettage effectiveness and the limited sample size., Discussion: The results support the view that PDT is a promising treatment approach for CNH., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the therapeutic potential of intra-articular hyaluronan-derivative HYADD® 4-G and/or platelet-rich plasma (PRP) in a mouse model of non-invasive joint injury., Methods: Non-invasive axial tibial loading was used to induce joint injury in 10-week-old C57BL/6J mice (n = 86). Mice underwent a single loading of either 6 Newton (N) or 9N axial tibial compression. HYADD® 4-G was injected intra-articularly at 8 mg/mL or 15 mg/mL either before or after loading with or without PRP. Phosphate-buffered-saline was injected as control. Knee joints were harvested at 5 or 56 days post-loading and prepared for micro-computed tomography scanning and subsequently processed for histology. Immunostaining was performed for aggrecan to monitor its distribution, for CD44 to monitor chondrocyte reactive changes and for COMP (cartilage oligomeric matrix protein) as an index for cartilage matrix changes related to loading and cartilage injury. TUNEL assay was performed to identify chondrocyte apoptosis., Results: Loading initiated cartilage proteoglycan loss and chondrocyte apoptosis within 5 days with slowly progressive post-traumatic osteoarthritis (no cartilage degeneration, but increased synovitis and ectopic calcification after 9N loading) at 56 days. Mice treated with repeated HYADD® 4-G (15 mg/mL) or HYADD® 4-G (8 mg/mL) ± PRP or PRP alone exhibited no significant improvement in the short-term (5 days) and long-term (56 days) consequences of joint loading except for a trend for improved bone changes compared to non-loaded joints., Conclusion: While we failed to show an overall effect of intra-articular delivery of hyaluronan-derivative and/or PRP in reversing/protecting the pathological events in cartilage and synovium following joint injury, some bone alterations were relatively less severe with hyaluronan-derivative at higher concentration or in association with PRP.

Background: Knee injuries are very common in some sports and particularly in soccer due to the highly repetitive loading of the mechanical stress involved in this practice. Knee-joint injuries account for 40% of all different kinds of lesions. Traumatic or degenerative patellofemoral or tibialfemoral chondropaties of knee cause disabling symptoms, joint pain and/or dysfunctions. The aim of the study was to evaluate the effects of HYADD4-G, a hydrogel based on a hyaluronic acid derivative, in professional soccer players affected by traumatic or degenerative knee chondropathy., Methods: Thirty male professional soccer players participants in the Italian League 2014-2015, affected by traumatic or degenerative knee patellofemoral (N.=12) or tibiofemoral (N.=18) chondropathy assessed through MRI and/or arthroscopy of knee joints and the ICRS staging (International Cartilage Repair Society ≤3a), were enrolled in this pilot prospective study. Patients underwent 2 intra-articular (IA) injections of HYADD4-G (3 mL of 8 mg/mL) at one week interval. Patients were prospectively evaluated at baseline and then at 1, 3 and 6 months after the treatment by the Osteoarthritis Outcome Score (KOOS) Score (main outcome) and by the Visual Analog Scale (VAS) to evaluate pain., Results: A significant improvement in all clinical endpoints from pretreatment to different times of evaluation was found in all patients. ANOVA with repeated measure using the SPSS has showed significantly better results in term of KOOS and VAS scores at 1, 3 and 6 months compared to the pre-injection value (P<0.05)., Conclusions: IA HYADD4-G is highly effective to improve resting and walking pain in professional male soccer players with traumatic or degenerative knee chondropathy.