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Diabetes mellitus (DM) is one of the prominent risk factors for pathological development and progression of tendinopathy. One feature of DM‐related changes in tendinopathy is accumulation of advanced glycation end products (AGEs) in affected tendons. Pioglitazone (Pio), a peroxisome proliferator‐activated receptor γ agonist, performs a protective effect against AGEs. The present study aimed to investigate the pathogenetic role of AGEs on tendon‐derived stem cells (TDSCs) and to determine the effect of Pio on AGEs‐induced TDSC dysfunctions. Results indicated that AGEs induced TDSC apoptosis as well as compensatory activation of autophagy. Pharmacologic activation/inhibition of autophagy leaded to alleviate/exacerbate apoptosis induced by AGEs. We further confirmed the effect of Pio on autophagy, which ameliorated apoptosis and abnormal calcification caused by AGEs both in vitro and in vivo. Thus, we suggest that Pio ameliorates the dysfunctions of TDSCs against AGEs by promoting autophagy, and we also reveal that Pio is a potential pharmacological choice for tendinopathy. [ABSTRACT FROM AUTHOR]

NR4A3 is a member of nuclear receptor subfamily 4, which is an important regulator of cellular function and inflammation. In this study, high expression of NR4A3 in human osteoarthritis (OA) cartilage was firstly observed. To explore the relationship between NR4A3 and OA, we used a lentivirus overexpression system to simulate its high expression and study its role in OA. Additionally, siRNA‐mediated knockdown of NR4A3 was used to confirm the findings of overexpression experiments. The results showed the stimulatory effect of IL‐1β on cartilage matrix‐degrading enzyme expression such as MMP‐3, 9, INOS and COX‐2 was enhanced in NR4A3‐overexpressed chondrocytes and decreased in NR4A3‐knockdown chondrocytes at both mRNA and protein levels, while IL‐1β‐induced chondrocyte‐specific gene (collagen 2 and SOX‐9) degradation was only regulated by NR4A3 at protein level. Furthermore, overexpression of NR4A3 would also enhance EBSS‐induced chondrocytes apoptosis, while knockdown of NR4A3 decreased apoptotic level after EBSS treatment. A pathway study indicated that IL‐1β‐induced NF‐κB activation was enhanced by NR4A3 overexpression and reduced by NR4A3 knockdown. We suggest that NR4A3 plays a pro‐inflammatory role in the development of OA, and we also speculate that NR4A3 mainly regulates cartilage matrix‐degrading gene expression under inflammatory conditions via the NF‐κB pathway. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic joint disease involving cartilage erosion and matrix degradation. Costunolide is a sesquiterpene lactone that has been demonstrated to exert anti-inflammatory activities in a wide variety of cells. The aim of the present study was to investigate the effect of costunolide in OA treatment, using rat chondrocytes and an OA rat model, in which animals were subjected to destabilization of the medial meniscus. The results revealed that costunolide (2–6 µM) had no effect on chondrocyte viability or phenotype maintenance. Costunolide decreased the interleukin (IL)-1β-induced upregulation of matrix metalloproteinases (MMPs), inducible nitric oxide synthase, cyclooxygenase-2 and IL-6, and increased the expression of collagen II and transcription factor SOX-9, which were inhibited by IL-1β. Costunolide significantly decreased p65 phosphorylation induced by IL-1β and the translocation of p65 into the nucleus of rat chondrocytes, as observed by western blot analysis and immunofluorescence staining. In addition, activation of the Wnt/β-catenin signaling pathway was inhibited by costunolide, as demonstrated by the level of activation of β-catenin and the transfer of β-catenin into the nucleus induced by IL-1β. In vivo, cartilage treated with costunolide exhibited attenuated degeneration and lower Mankin scores compared with the OA group. The present study investigated the anti-osteoarthritic effects of costunolide, which exerted anti-inflammatory activities and inhibited MMPs expression. Taken together, these results indicate that costunolide may have a potential value in the treatment of OA. [ABSTRACT FROM AUTHOR]

Tendon injuries are common and require a long time to heal, and are particularly associated with some adverse problems such as adhesion and rupture. Herein, we aim to develop new bioactive scaffolds endowed with stem cell sheets and growth factors to enable cell migration and proliferation favorable for tendon regeneration in situ. An exogenous basic fibroblast growth factor (bFGF)-loaded fibrin gel was firstly incorporated into the porous network of knitted poly(lactide-co-glycolide) (PLGA) scaffolds and then sheets of mesenchymal stem cells (MSCs) were also integrated into the scaffolds. It was shown that the pores in the knitted PLGA scaffold were readily filled with a complex network of fibrin fiber gel and the fibrin fibers were beneficial for the controlled release of bFGF over a long time period. After transplantation in a critical-size Achilles tendon defect model (7 mm) in the rat right hindlimb, gross observation revealed no immunologic incompatibility or rejection derived from the scaffold systems. It was observed that the MSC sheets contributed directly to tendon regeneration, and exerted an environment-modifying effect on the injuries in situ, consistent with the beneficial effect of bFGF. It was interesting that the knitted PLGA–fibrin gel scaffolds loaded with MSC sheets and bFGF showed the highest expression of tendon-related gene markers and outstanding repair efficacy, including appreciable biomechanical strength and native-like histological microstructures. Therefore, the integration of MSC sheets and bFGF into PLGA/bFGF–fibrin gel scaffolds may stimulate the proliferation and tenogenic differentiation of MSCs in situ and synergistically enhance the injured tendon reconstruction. [ABSTRACT FROM AUTHOR]

Abstract: Metabolism of bone is regulated by the balance between osteoblast‐mediated bone formation and osteoclast‐mediated bone resorption. Activation of osteoclasts could lead to osteoporosis. Thus, inhibiting the activity of osteoclasts becomes an available strategy for the treatment of osteoporosis. Tectorigenin is an extract of Belamcanda chinensis In the present study, the anti‐osteoclastogenesis effects of tectorigenin were investigated in vitro and in vivo. The results showed preventive and therapeutic effects of tectorigenin at concentrations of 0, 10, 40, and 80 μmol/L in the maturation and activation of osteoclasts. A signalling study also indicated that tectorigenin treatment reduces activation of NF‐κB signalling in osteoclastogenesis. Animal experiment demonstrated that tectorigenin treatment (1‐10 mg/kg, abdominal injection every 3 days) significantly inhibits bone loss in ovariectomized C57BL/6. Our data suggest that tectorigenin is a potential pharmacological choice for osteoporosis. [ABSTRACT FROM AUTHOR]

As a chronic disease, osteoarthritis (OA) leads to the degradation of both cartilage and subchondral bone, its development being mediated by proinflammatory cytokines like interleukin-1β. In the present study, the anti-inflammatory effect of specnuezhenide (SPN) in OA and its underlying mechanism were studied in vitro and in vivo. The results showed that SPN decreases the expression of cartilage matrix-degrading enzymes and the activation of NF-κB and wnt/β-catenin signaling, and increases chondrocyte-specific gene expression in IL-1β-induced inflammation in chondrocytes. Furthermore, SPN treatment prevents the degeneration of both cartilage and subchondral bone in a rat model of OA. To the best of our knowledge, this study is the first to report that SPN decreases interleukin-1β-induced inflammation in rat chondrocytes by inhibiting the activation of the NF-κB and wnt/β-catenin pathways, and, thus, has therapeutic potential in the treatment of OA. [ABSTRACT FROM AUTHOR]

Pyruvate kinase M2 (PKM2) has been wildly verified to modulate glycolysis in tumor cells. However, the role of PKM2 on the glycolysis of osteoarthritis (OA) chondrocytes is still unclear. In present study, we investigate the function of PKM2 on OA chondrocyte glycolysis and the collagen matrix generation in vitro. Results showed that PKM2 was upregulated in OA chondrocytes compared with healthy control chondrocytes. In OA chondrocytes, ATP expression was lower compared with healthy control chondrocytes. Loss-of-function experiment showed that PKM2 knockdown mediated by lentivirus transfection could significantly suppress the glucose consumption and lactate secretion levels and decrease glucose transporter-1 (Glut-1), lactate dehydrogenase A (LDHA), and hypoxia inducible factor 1-alpha (HIF-1α), indicating the inhibition of PKM2 knockdown on glycolysis. Moreover, Cell Counting Kit-8 (CCK-8), flow cytometry, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay showed that PKM2 knockdown inhibited OA chondrocyte proliferation and promoted the apoptosis. Western blot and immunocytochemical staining showed that PKM2 knockdown downregulated the expression levels of COL2A1 and SOX-9. In summary, our results conclude that PKM2 modulates the glycolysis and extracellular matrix generation, providing the vital role of PKM2 on OA pathogenesis and a novel therapeutic target for [ABSTRACT FROM AUTHOR]

Background: Chronic tendinopathy is a commonly occurring clinical problem that affects both athletes and inactive middle-aged patients. Although some studies have shown that different platelet-rich plasma (PRP) preparations could exert various therapeutic effects in vitro, the role of leukocytes in PRP has not yet been defined under tendinopathy conditions in vivo. Purpose: This study compared the effects of the intratendon delivery of leukocyte-poor PRP (Lp-PRP) versus leukocyte-rich PRP (Lr-PRP) in a rabbit chronic tendinopathy model in vivo. Study Design: Controlled laboratory study. Methods: Four weeks after a local injection of collagenase in the Achilles tendon, the following treatments were randomly administered on the lesions: injections of (1) 200 μL of Lp-PRP (n = 8), (2) 200 μL of Lr-PRP (n = 8), or (3) 200 μL of saline (n = 8). Healing outcomes were assessed at 4 weeks after therapy with magnetic resonance imaging (MRI), cytokine quantification, real-time polymerase chain reaction analysis of gene expression, histology, and transmission electron microscopy (TEM). Results: MRI revealed that the Lr-PRP and saline groups displayed higher signal intensities compared with the Lp-PRP group with T2 mapping. Histologically, the Lp-PRP group displayed significantly better general scores compared with the Lr-PRP (P = .001) and saline (P < .001) groups. Additionally, TEM showed that the Lp-PRP group had larger collagen fibril diameters than the Lr-PRP group (P < .001). Enzyme-linked immunosorbent assay showed a significantly lower level of catabolic cytokine IL-6 in the Lp-PRP group compared with the Lr-PRP (P = .001) and saline (P = .021) groups. The Lp-PRP group displayed significantly increased expression of collagen I compared with the saline group (P = .004) but not the Lr-PRP group. Both the Lp-PRP and Lr-PRP groups exhibited significantly lower matrix metalloproteinase (MMP)–1 and MMP-3 expression levels compared with the saline group. However, only the Lp-PRP group displayed significantly higher expression of TIMP-1 than the saline group (P = .024). Conclusion: Compared with Lr-PRP, Lp-PRP improves tendon healing and is a preferable option for the clinical treatment of tendinopathy. Clinical Relevance: PRP is widely used in the clinical management of chronic tendinopathy. However, the clinical results are ambiguous. It is imperative to understand the influence of leukocytes on PRP-mediated tissue healing in vivo, which could facilitate the better clinical management of chronic tendinopathy. Further studies are needed to translate our findings to the clinical setting. [ABSTRACT FROM AUTHOR]

Background: Lumbar disc removal is currently the standard treatment for lumbar disc herniation. No consensus has been achieved whether aggressive disc resection with curettage (discectomy) versus conservative removal of the offending disc fragment alone (sequestrectomy) provides better outcomes. This study aims to compare the reherniation rate and clinical outcomes between discectomy and sequestrectomy by literature review and a meta-analysis. Methods: A systematic search of PubMed, Medline, Embase and the Cochrane Library was performed up to June 1, 2014. Outcomes of interest assessing the two techniques included demographic and clinical baseline characteristics, perioperative variables, complications, recurrent herniation rate and post-operative functional outcomes. Results: Twelve eligible trials evaluating discectomy vs sequestrectomy were identified including one randomized controlled study, five prospective and six retrospective comparative studies. By contrast to discectomy, sequestrectomy was associated with significantly less operative time (p<0.001), lower visual analogue scale (VAS) for low back pain (p<0.05), less post-operative analgesic usage (p<0.05) and better patients’ satisfaction (p<0.05). Recurrent herniation rate, reoperation rate, intraoperative blood loss, hospitalization duration and VAS for sciatica were without significant difference. Conclusions: According to our pooled data, sequestrectomy entails equivalent reherniation rate and complications compared with discectomy but maintains a lower incidence of recurrent low back pain and higher satisfactory rate. High-quality prospective randomized controlled trials are needed to firmly assess these two procedures. [ABSTRACT FROM AUTHOR]

Background: The revision rate of articular surface replacement (ASR) implants continues to rise in China because of metal debris. However, there are few reports on the clinical results of ASR implants with prolonged follow-up time in China. This study investigated the clinical outcomes and the risk factors of revision surgery in patients with ASR implants. Methods: In total, 74 patients (74 hips) who underwent primary total hip arthroplasty (THA) with ASR implants over the past 4 to 10 years were retrospectively analyzed. Relevant clinical, radiographic, and biochemical data were examined. Results: The average follow-up time was 88.46 (range 23–114) months, and the ASR implants of 18 hips (24.3%) were revised. Patients who received revision surgery had worse joint function with significantly lower Harris Hip Score and Western Ontario and McMaster Universities index than non-revision patients (61.11 ± 6.68 vs 85.30 ± 9.16, p < 0.001; 61.00 ± 3.83 vs 79.04 ± 14.49, p < 0.001; respectively). Higher acetabular abduction angle and serum Co and Cr concentration were significantly relevant to worse joint function as measured by HSS (p = 0.018, 0.009, 0.043, respectively). ROC curve analysis was applied to categorize the optimal cutoff values of acetabular abduction angle and serum Cr and Co concentration for revision surgery, which were settled as 47.80°, 98.44 μg/L, and 6.95 μg/L, respectively. Overall survival of the prostheses with high acetabular abduction angle (> 47.80°, HR = 70.145, 95% CI 1.558–3158.213, p = 0.029), high serum Cr concentration (98.44 μg/L, HR = 58.956, 95% CI 1.294–2685.203, p = 0.036), and high serum Co concentration (> 6.95 μg/L, HR = 179.511, 95% CI 2.360–13656.941, p = 0.019) decreased significantly than the lower groups. Conclusions: Evaluation of the DePuy ASR XL articulation demonstrated increased rates of revision following a longer follow-up period. High acetabular abduction angle and serum Cr and Co concentration correlated with worse clinical outcomes and high revision rate. Therefore, we advocate that patients with DePuy ASR XL implants be followed up more closely than those with other implants, especially with high acetabular abduction angle and serum Cr or Co concentration. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is one of the most common chronic musculoskeletal disorder worldwide, representing a major source of disability, pain and socioeconomic burden. Yet the effective pharmaceutical treatments applied in the clinical works are merely symptomatic management with uncertainty around their long-term safety and efficacy, namely no drugs currently are capable of modulating the biological progression of OA. Here, we identified the potent anti-inflammatory as well as anti-oxidative properties of Nitidine Chloride (NitC), a bioactive phytochemical alkaloid extracted from natural herbs, in IL-1β-treated rat articular chondrocytes (RACs), LPS-stimulated RAW 264.7 and rat osteoarthritic models in vivo . We demonstrated NitC remarkably inhibited the production of inflammatory mediators including COX2 and iNOS, suppressed the activation of MAPK and NF-κB cell signaling pathway and reduced the expression of extracellular matrix (ECM) degrading enzymes including MMP3, MMP9 and MMP13 in IL-1β-treated RACs. Several emerging bioinformatics tools were performed to predict the underlying mechanism, the result of which indicated the potential reactive oxygen species (ROS) clearance potential of NitC. Further, NitC exhibited its anti-oxidative potential through ameliorating cellular senescence in IL-1β-treated RACs and decreasing NLRP3 inflammasomes activation in LPS-stimulated RAW 264.7 via scavenging ROS. Additionally, X-ray, micro-CT and other experiments in vivo demonstrated that intra-articular injection of NitC significantly alleviated the cartilage erosion, ECM degradation and subchondral alterations in OA progression. In conclusion, the present study reported the potent anti-inflammatory and anti-oxidative potential of NitC in OA biological process, providing a promising therapeutic agent for OA management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Ge, Tang, He, Moqbel, Xu, Ma, Zhou, Ran and Wu.)

Articular cartilage focal lesion remains an intractable challenge in sports medicine, and autologous chondrocytes' implantation (ACI) is one of the most commonly utilized treatment modality for this ailment. However, the current ACI technique requires two surgical steps which increases patients' morbidity and incurs additional medical costs. In the present study, we developed a one-step cryopreserved off-the-shelf ACI tissue-engineered (TE) cartilage by seeding pellets of spheroidal cartilage stem/progenitor cells (CSPCs) on a silk scaffold. The pellets were developed through a hanging-drop method, and the incubation time of 1 day could efficiently produce spheroidal pellets without any adverse influence on the cell activity. The pellet size was also optimized. Under chondrogenic induction, pellets consisting of 40 000 CSPCs were found to exhibit the most abundant cartilage matrix deposition and the highest mRNA expression levels of SOX9, aggrecan, and COL2A1, as compared with pellets consisting of 10 000, 100 000, or 200 000 CSPCs. Scaffolds seeded with CSPCs pellets containing 40 000 cells could be preserved in liquid nitrogen with the viability, migration, and chondrogenic ability remaining unaffected for as long as 3 months. When implanted in a rat trochlear cartilage defect model for 3 months, the ready-to-use, cryopreserved TE cartilage yielded fully cartilage reconstruction, which was comparable with the uncryopreserved control. Hence, our study provided preliminary data that our off-the-shell TE cartilage with optimally sized CSPCs pellets seeded within silk scaffolds exhibited strong cartilage repair capacity, which provided a convenient and promising one-step surgical approach to ACI.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by deterioration of articular cartilage. Dual specificity phosphatase 5 (DUSP5), a member of the DUSP subfamily, is known to regulate cellular inflammation. Here, we studied the relationship between DUSP5 and OA by knockdown and overexpression DUSP5, respectively. Results from in vitro experiments demonstrated that the knockdown of DUSP5 increased interleukin-1β (IL-1β)-induced expression of inflammatory genes, such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2), and matrix metalloproteinases (MMPs) in chondrocytes, whereas it decreased the expression of anti-inflammatory genes, such as tissue inhibitor of metalloproteinase 3 (TIMP3) and IL-10. Conversely, the overexpression of DUSP5 suppressed the IL-1β-induced expression of iNOS, COX-2, and MMPs, and upregulated the expression of TIMP3 and IL-10. Moreover, knockdown of DUSP5 enhanced the IL-1β-induced activation of NF-κB and ERK pathways, whereas its overexpression inhibited these pathways. DUSP5 overexpression prevented cartilage degeneration in a rat OA model, while its knockdown reversed that effect. Our findings reveal that DUSP5 suppresses IL-1β-induced chondrocyte inflammation by inhibiting the NF-κB and ERK signaling pathways and ameliorates OA.

Tendinopathy is a common musculoskeletal disorder that mainly affects athletes and people of older age. Tumor necrosis factor-α (TNF-α) plays an important role in initiating tendinopathy. Tectorigenin, an extract component of Belam-canda Chinesis , possesses anti-inflammatory and anti-apoptosis activity. The present study was established to investigate the role of tectorigenin against the pathogenetic effects of TNF-α on tendon-derived stem cells (TDSCs) in vivo and in vitro . The findings indicated that TNF-α is able to induce TDSC inflammation, apoptosis, and ossification, as well as activate nuclear factor-kappa B and mitogen-activated protein kinase (MAPK). Furthermore, the results confirmed that tectorigenin is able to inhibit the TNF-α-induced inflammation, apoptosis, and ossification. Tectorigenin treatment decreases activation of NF-kappa B and MAPK signaling in TDSCs. Tectorigenin ameliorates tendinopathy in the in vivo rat model. Thus, these data reveal that tectorigenin can serve as a potential treatment for tendinopathy., (Copyright © 2020 Moqbel, Xu, Chen, Xu, He, Wu, Ma, Ran, Wu and Xiong.)

Synovial inflammation is a major pathological feature of osteoarthritis (OA), which is a chronic degenerative joint disease. Fibroblast-like synoviocytes (FLS), localized in the synovial membrane, are specialized secretory cells. During OA synovitis, FLS produce chemokines and cytokines that stimulate chondrocytes to secrete inflammatory cytokines and activate matrix metalloproteinases (MMPs) in FLS. Recent studies have demonstrated that sirtuin 3 (SIRT3) performs as a key regulator in maintaining mitochondrial homeostasis in OA. This study aims at ascertaining whether SIRT3 is involved in OA synovitis. The overexpression (OE) and knockdown (KD) of SIRT3 are established by short hairpin RNA (shRNA) and recombinant plasmid in human FLS. The anti-inflammatory effect of SIRT3 underlying in oleanolic acid- (OLA-) prevented interleukin-1 β - (IL-1 β -) induced FLS dysfunction is then evaluated in vitro. Additionally, the molecular mechanisms of SIRT3 are assessed, and the interaction between SIRT3 and NF- κ B is investigated. The data suggested that SIRT3 can be detected in human synovial tissues during OA, and OLA could elevate SIRT3 expression. OE-SIRT3 and OLA exhibited equal authenticity to repress inflammation and reverse oxidative stress changes in IL-1 β -induced human FLS dysfunction. KD-SIRT3 was found to exacerbate inflammation and oxidative stress changes in human FLS. Furthermore, it was found that SIRT3 could directly bind with NF- κ B, resulting in the suppression of NF- κ B activation induced by IL-1 β in human FLS, which then repressed synovial inflammation in OA. In general, the activation of SIRT3 by OLA inhibited synovial inflammation by suppressing the NF- κ B signal pathway in FLS, and this suggested that SIRT3 is a potential target for OA synovitis therapy., Competing Interests: All authors declare that they have no competing interests., (Copyright © 2020 Jiapeng Bao et al.)

Osteoarthritis (OA) is the most prevalent joint disease and uncontrolled inflammation is now recognized to play vital roles in OA development. Targeting the endogenous counterpart of inflammation may develop new therapeutic approaches in resolving inflammation persistence and treating inflammatory disease including OA. The orphan nuclear receptor 4A1 (NR4A1) is a key negative regulator of inflammatory responses but its role in osteoarthritis remains unclear. In the present study, we found that the NR4A1 expression was elevated in human osteoarthritis cartilage and in vitro OA model, which could be blocked by NF-κB signal inhibitor JSH23. The overexpression of NR4A1 inhibited, whereas knockdown of NR4A1 enhanced IL-1β induced COX-2, iNOS, MMP3, MMP9 and MMP13 expression, and luciferase reporter activity of NF-κB response element. Though NR4A1 was upregulated in inflammatory stimulation and creates a negative feedback loop, persistent inflammatory stimulation inhibited NR4A1 expression and activation. The expression of NR4A1 declined rapidly after an initial peak in conditions of chronic IL-1β stimulation, which could be partially restored by HDACs inhibitor SAHA. The phosphorylation of NR4A1 was increased in human osteoarthritis cartilage, and p38 inhibitor SB203580, JNK inhibitor SP600125 and ERK inhibitor FR180204 could significantly inhibited IL-1β induced NR4A1 phosphorylation. Reactivation of NR4A1 by its agonist cytosporone B could inhibit IL-1β induced chondrocyte inflammation and expression of COX-2, iNOS, MMP3, MMP9, and MMP13. In rat OA model, intra-articular injection of cytosporone B protected cartilage damage and ameliorated osteoarthritis. Thus, our study demonstrated that the NR4A1 is a key endogenous inhibitor of chondrocyte inflammation, which was relatively inactivated under chronic inflammatory stimulation through HDACs mediated transcriptional suppression and MAKP dependent phosphorylation in osteoarthritis. NR4A1 agonist cytosporone B could reactivate and restore the inhibitory regulatory ability of NR4A1, prevent excessive inflammation, and ameliorates osteoarthritis., (Copyright © 2020 Xiong, Ran, Xu, Tong, Adel Abdo, Ma, Xu, He, Wu, Chen, Hu, Jiang, Bao, Chen and Wu.)

Osteoarthritis (OA) is a chronic degenerative joint disease, related to the overexpression of matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), inflammation, and chondrocyte apoptosis. Nesfatin-1 is an adipokine, which plays an important role in the development of OA, especially in obese people. In the present study, cartilage degradation and apoptosis observed in OA patients was evaluated. Furthermore, the anti-inflammatory and anti-apoptotic effects of nesfatin-1, and its underlying in vitro and in vivo mechanisms were investigated. The results showed that nesfatin-1 increased significantly the expression of collagen type II alpha 1 chain (Col2a1), and reduced the expression of MMPs, ADAMTS5, cyclooxygenase (COX)-2, caspase-3, nitric oxide (NO), inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), interleukin (IL)-6, and chondrocyte apoptosis rate, which may be induced by IL-1β in rat chondrocytes. Furthermore, nesfatin-1 treatment prevented cartilage degeneration in the rat OA model. It was found that nesfatin-1 suppressed the IL-1β-induced activation of NF-κB, the mitogen-activated protein kinase (MAPK), and the Bax/Bcl-2 signal pathway in chondrocytes. These results suggest that in vivo nesfatin-1 could play a protective role in the development of OA and can be potentially used for its treatment.

Background: Osteoarthritis (OA) is one of the most important age-related degenerative diseases, and the leading cause of disability and chronic pain in the aging population. Recent studies have identified several lncRNA-associated functions involved in the development of OA. Because age is a key risk factor for OA, we investigated the differential expression of age-related lncRNAs in each stage of OA., Methods: Two gene expression profiles were downloaded from the GEO database and differentially expressed genes (DEGs) were identified across each of the different developmental stages of OA. Next, gene ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the function of the DEGs. Finally, a lncRNA-targeted DEG network was used to identify hub-lncRNAs., Results: A total of 174 age-related DEGs were identified. GO analyses confirmed that age-related degradation was strongly associated with cell adhesion, endodermal cell differentiation and collagen fibril organization. Significantly enriched KEGG pathways associated with these DEGs included the PI3K-Akt signaling pathway, focal adhesion, and ECM-receptor interaction. Further analyses via a protein-protein interaction (PPI) network identified two hub lncRNAs, CRNDE and LINC00152, involved in the process of age-related degeneration of articular cartilage. Our findings suggest that lncRNAs may play active roles in the development of OA. Investigation of the gene expression profiles in different development stages may supply a new target for OA treatment., Competing Interests: The authors declare there are no competing interests.

BACKGROUND The study aimed to develop a novel orthopedic surgical scaffold made of collagen and silk to repair the tendon and bone interface, and to investigate its influence on tendon and bone healing in a rabbit model. MATERIAL AND METHODS Four types of surgical scaffold were prepared, including a random collagen scaffold (RCS), an aligned collagen scaffold (ACS), a random collagen scaffold combined with knitted silk (RCSS), and an aligned collagen scaffold combined with knitted silk (ACSS). Rabbit bone marrow stem cells (BMSCs) were cultured and seeded onto the RCS and ACS scaffold. The animal model included four-month-old female New Zealand White rabbits (N=20) that underwent drilling into the rotator cuff of the left supraspinatus muscle tendon, randomized into the ACSS and RCSS groups. RESULTS Rabbit BMSCs adhered to and proliferated on the RCS and ACS in vitro. Transcription levels of the COL I, COL III, and tenascin (TCN) genes were significantly increased in the ACS group compared with the RCS group. Transcription levels of COL I, runt-related transcription factor-2 (RUNX-2) and bone morphogenetic protein-2 (BMP-2) were significantly increased in the RCS group compared with the ACS group. RCSS and ACSS implanted in the rabbit models for eight weeks resulted in more regenerative tissue in the RCSS group compared with the ACSS group, with new cartilage at the tendon and bone interface at 12 weeks. CONCLUSIONS A collagen and silk scaffold improved healing of the tendon and bone interface in a rabbit model.

To investigate the inflammatory effect of Interleukin 18 (IL-18) on rat chondrocytes and the involvement of Wnt/β-catenin and Hedgehog pathways, the mRNA and protein level of matix-degrading enzymes (MMP-2, 3, 9,13 and aggrecanses) and chondrocyte-specific proteins (Collagen II and aggrecan) were evaluated by qRT-PCR and Western blot, and key protein level of Wnt/β-catenin and Hedgehog pathways including β-catenin, GSK-3β, DKK-1, IHH, SHH, and Gli-2 were evaluated by Western blot. Dickkopf-1 (DKK-1) and Cyclopamine were used as antagonist of Wnt/β-catenin and Hedgehog pathways to perform pathway inhibition tests. In addition, location and expression of β-catenin, GSK-3β, Gli-2 and Smo were assessed by Immunofluorescence microscopy. The results showed up-regulation of matix-degrading enzymes (MMP-2, 3, 9,13 and aggrecanses) and down-regulation of chondrocyte-specific proteins (Collagen II and aggrecan) at both mRNA and protein level and activation of Wnt/β-catenin and Hedgehog pathways in the inflammatory reaction on rat chondrocytes caused by IL-18 treatment was observed. As conclusion, Wnt/β-catenin and Hedgehog pathways are involved in the inflammatory effect of IL-18 in vitro ., Competing Interests: CONFLICTS OF INTEREST All authors have no conflicts of interest.