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Aims: To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration. Methods: The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm2, 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens. Results: In the histopathological analysis, the macro-morphological grading scale showed a significant increase, while the histological score and cartilage repair scale of ESWT exhibited a significant decrease compared to OCD at the 8- and 12-week timepoints. At the 12-week follow-up, ESWT exhibited a significant improvement in the volume of damaged bone compared to OCD. Furthermore, immunohistochemistry analysis revealed a significant decrease in type I collagen and a significant increase in type II collagen within the newly formed hyaline cartilage following ESWT, compared to OCD. Finally, SRY-box transcription factor 9 (SOX9), aggrecan, and TGF-β, BMP-2, -3, -4, -5, and -7 were significantly higher in ESWT than in OCD at 12 weeks. Conclusion: ESWT promoted the effect of TGF-β/BMPs, thereby modulating the production of extracellular matrix proteins and transcription factor involved in the regeneration of articular cartilage and subchondral bone in an OCD rat model. Cite this article: Bone Joint Res 2024;13(7):342–352.

Background: Extracorporeal shockwave therapy (ESWT) and adipose-derived mesenchymal stem cells (ADSCs) have been used clinically for the treatment of osteonecrosis of the femoral head (ONFH). The study elucidated that ESWT, ADSCs, and combination therapy modulated pro-inflammatory cytokines in the articular cartilage and subchondral bone of early rat ONFH. Methods: ESWT and ADSCs were prepared and isolated for treatment. Micro-CT, pathological analysis, and immunohistochemistry were performed and analysed. Results: After treatments, subchondral bone of ONFH was improved in trabecular bone volume (BV/TV) (p < 0.001), thickness (Tb.Th) (p < 0.01 and 0.001), and separation (Tb.Sp) (p < 0.001) and bone mineral density (BMD) (p < 0.001) using micro-CT analysis. The articular cartilage was protected and decreased apoptosis markers after all the treatments. The expression of IL33 (p < 0.001), IL5 (p < 0.001), IL6 (p < 0.001), and IL17A (p < 0.01) was significantly decreased in the ESWT, ADSCs, and Combination groups as compared with ONFH group. The IL33 receptor ST2 was significantly increased after treatment (p < 0.001) as compared with ONFH group. The Combination group (p < 0.01) decreased the expression of IL6 better than the ESWT and ADSCs groups. Conclusion: ESWT, ADSCs and combination therapy significantly protected articular cartilage and subchondral bone of early rat ONFH by modulating the expression of pro-inflammatory cytokines including, IL33 and its receptor ST2, IL5, IL6, and IL17A.

Abstract Background Acromioclavicular joint (ACJ) dislocation is a relatively common shoulder injury. For the treatment of cases of severe ACJ dislocation (Rockwood type III–V), hook plate fixation is an easy-to-master and minimally-invasive approach to surgical intervention. Over stress on the acromion following hook plate fixation often leads to acromial complications such as osteolysis and loss of reduction. We hypothesized that suspensory reconstruction alongside hook plate fixation might provide a superior stability and reduce complications as compared with hook plate fixation alone. The purpose of the study was to assess the clinical and radiographic outcomes of these two surgical modalities. Methods We retrospectively enrolled 49 patients with acute ACJ dislocation from May 2010 to December 2018. Among them, 19 patients received hook plate fixation only (HP group), and 19 underwent concomitant hook plate fixation and loop suspension fixation with two mersilene sutures (HM group). The demographic data of the patients were recorded and analyzed. All patients underwent a shoulder X-ray initially, immediately postoperatively, and at 1, 3, 6 and 12 months to measure the relative coracoclavicular distance (rCCD). Clinical assessment of shoulder function outcome was conducted using the Constant Murley Score (CMS); the University of California at Los Angeles (UCLA) Shoulder Score was also measured at the latest follow-up. Results There were no significant differences in the demographic data between the two groups. With regards to the CMS and the UCLA score, the HM group and HP group both had excellent outcomes, and no significant differences in scores were observed between groups (CMS: 93.90 ± 6.16 versus 94.47 ± 7.26, p = 0.47; UCLA score: 32.84 ± 2.91 versus 34.32 ± 1.16, p = 0.07). However, the HM group demonstrated substantial superiority in terms of maintenance of the rCCD over the HP group (91.47 ± 27.47 versus 100.75 ± 48.70, p = 0.015). In addition, there was less subacromial osteolysis in the HM group than the HP group (52.6% versus 15.8%, p = 0.038). Conclusion Both fixations yielded excellent functional outcomes. However, concomitant hook plate fixation with loop suspensory reconstruction demonstrated the fewer acromion complications and statistical differences in reduction maintenance with less clinical significance.

Abstract Background VP1 of the chicken anemia virus (CAV) is a structural protein that is required for virus encapsulation. VP1 proteins are present both in the nucleus and cytoplasm; however, the functional nuclear localization signal (NLS) and nuclear export signal (NES) of VP1 are still unknown. This study aimed to characterize the NLS and NES motifs of VP1 using bioinformatics methods and multiple-site fragment deletions, and investigate shuttling of VP2 from nucleus to cytoplasm by co-transfection with VP1. Methods Two putative NLS motifs were predicted by the WoLF PSORT and NLStradamus programs from the amino acid sequence of VP1. Three NES motifs of VP1 were predicted by the NetNES 1.1 Server and ELM server programs. All mutants were created by multiple-site fragment deletion mutagenesis. VP1 and VP2 were co-expressed in cells using plasmid transfection. Results A functional NLS motif was identified at amino acid residues 3 to 10 (RRARRPRG) of VP1. Critical amino acids 3 to 10 were significantly involved in nuclear import in cells and were evaluated using systematic deletion mutagenesis. Three NES motifs of VP1 were predicted by the NetNES 1.1 Server and ELM server programs. A functional NES was identified at amino acid residues 375 to 388 (ELDTNFFTLYVAQ). Leptomycin B (LMB) treatment demonstrated that VP1 export from nucleus to cytoplasm occurred through a chromosome region maintenance 1 (CRM1)-dependent pathway. With co-expression of VP1 and VP2 in cells, we observed that VP1 may transport VP2 from nucleus to cytoplasm. Conclusion Our data showed that VP1 of CAV contained functional NLS and NES motifs that modulated nuclear import and export through a CRM1-dependent pathway. Further, VP1 may play a role in the transport of VP2 from nucleus to cytoplasm.

Purpose: Tension band wiring technique has been widely used for treating patellar fracture. Conventional techniques are associated with some complications and several modifications have been introduced to increase stabilization. The purpose of this study was to compare two different fixation techniques, the one-end and both-ends Kirschner wire bending fixation methods. Methods: We retrospectively reviewed patient data from 2013 to 2017, including the age, sex, body height, body weight, BMI, lesion of injury, trauma mechanism, fracture displacement and classification, type of fixation, fracture healing duration, length of follow-up, clinical results and complications. The surgical outcome was assessed using the pain score (VAS), Lysholm knee score, and knee joint ROM. Plain radiographs were used to evaluate radiographic outcomes and assess the fracture union duration and hardware complications. We performed statistical analysis to compare these two different fixation techniques. Results: There were no significant differences between the two groups in terms of demographic data, fracture healing duration, level of the K-wires, distance between the K-wires, or length of the K-wires over the patella length (all p > 0.05). There were significant differences in the VAS score, K-wire migration, flexion degree, ROM, and Lysholm score (all p < 0.001) between the two different fixation methods. Conclusion: The both-ends K-wire bending fixation method has a lower complication rate and results in a better clinical outcome than the one-end K-wire bending fixation method. This revised technique can effectively control both ends of the K-wires, thus eliminating the possibility of K-wire migration and improving the fixation stability.

Avascular necrosis (AVN) of the femoral head (AVNFH) is a disease caused by injury to the blood supply of the femoral head, resulting in a collapse with osteonecrosis and damage to the articular cartilage. Extracorporeal shockwave therapy (ESWT) has been demonstrated to improve AVNFH owing to its anti-inflammation activity, angiogenesis effect, and tissue regeneration in clinical treatment. However, there are still so many pieces of the jigsaw that need to be fit into place in order to ascertain the mechanism of ESWT for the treatment of AVNFH. The study demonstrated that ESWT significantly protected the trabecular bone volume fraction BV/TV (P

The dose-dependent effects of adipose-derived mesenchymal stem cell-conditioned medium (ADSC-CM) were compared with those of shockwave (SW) therapy in the treatment of early osteoarthritis (OA). Anterior cruciate ligament transaction (ACLT) with medial meniscectomy (MMx) was performed in rats divided into sham, OA, SW, CM1 (intra-articular injection of 100 μL ADSC-CM into knee OA), and CM2 (intra-articular injection of 200 μL ADSC-CM) groups. Cartilage grading, grading of synovium changes, and specific molecular analysis by immunohistochemistry staining were performed. The OARSI and synovitis scores of CM2 and SW group were significantly decreased compared with those of the OA group (p < 0.05). The inflammatory markers interleukin 1β, terminal deoxynucleotidyl transferase dUTP nick end labeling and matrix metalloproteinase 13 were significantly reduced in the CM2 group compared to those in the SW and CM1 groups (p < 0.001). Cartilage repair markers (type II collagen and SRY-box transcription factor 9, SOX9) expression were significantly higher in the CM2 group than in the other treatment groups (p < 0.001; p < 0.05). Furthermore, inflammation-induced growth factors such as bone morphogenetic protein 2 (BMP2), BMP5, and BMP6 were significantly reduced in the treatment groups, and the CM2 group showed the best results among the treatments (p < 0.05). In conclusion, ADSC-CM and SW ameliorated the expression of inflammatory cytokines and inflammation-induced BMPs to protect the articular cartilage of the OA joint.

Purpose: Femoral head fracture dislocations are serious articular fractures that are associated with soft tissue injuries and are challenging to treat. Arthroscopic surgery may be a way to treat fracture reduction and fixation, thereby avoiding the need for extensive arthrotomy. Methods: We followed up a consecutive series of seven patients with femoral head fracture dislocation via a scope-assisted percutaneous headless screw fixation between 2016 and 2017. The clinical and radiological results were assessed. Results: The locations of the fracture were all involving infra-foveal area. The mean follow-up duration was 18 (range 12–24) months. The mean Harris hip score was 90.8 (range 88–93) at the latest follow-up. None of the patients showed early osteoarthritis, heterotopic ossification, or avascular necrosis. The average maximal displacement of the fracture site was improved from preoperative 6.79 mm (range 4.21–12.32) to postoperative 2.76 mm (range 0.97–3.97). Concomitant intra-articular hip lesions secondary to traumatic hip dislocation can also be treated. Conclusion: Managing the infra-foveal fracture of the femoral head using arthroscopic reduction and fixation with headless screws can be a safe and minimally invasive option. More patients and longer follow-up are needed for a definite conclusion.

Adipose-derived mesenchymal stem cells (ADSCs) and shockwave (SW) therapy have been shown to exert a chondroprotective effect for osteoarthritis (OA). The results of this study demonstrated that autologous ADSCs had dose-dependent and synergistic effects with SW therapy (0.25 mJ/mm2 with 800 impulses) in OA rat knee joint. Autologous, high-dose 2 × 106 ADSCs (ADSC2 group) combined with SW therapy significantly increased the bone volume, trabecular thickness, and trabecular number among in the treatment groups. ADSC2 combined with SW therapy significantly reduced the synovitis score and OARSI score in comparison with other treatments. In the analysis of inflammation-induced extracellular matrix factors of the articular cartilage in OA, the results displayed that ADSC2 combined with SW therapy had a greater than other treatments in terms of reducing tumor necrosis factor-inducible gene (TSG)-6 and proteoglycan (PRG)-4, in addition to increasing tissue inhibitor matrix metalloproteinase (TIMP)-1 and type II collagen. Furthermore, ADSC2 combined with SW therapy significantly reduced the expression of inflammation-induced bone morphogenetic protein (BMP)-2 and BMP-6. Therefore, the results demonstrated that ADSC2 combined with SW therapy had a synergistic effect to ameliorate osteoarthritic pathological factors in OA joints.

Osteoporosis (OP) causes bone loss and weakness, increasing the risk of bone fracture. In this study, rats were divided into Sham, OP, SW(F) (0.25 mJ/mm2 with 1600 impulses to the left medial femur), and SW(T) (0.25 mJ/mm2 with 1600 impulses to the left medial tibia). The bone strength results following SW(T) were better than SW(F) in the modulus, extension at peak load, handleability, and strain at break. SW(T) had the best prevention for bone loss in both lower limbs of ovariectomized (OVX) rats. The cartilage cellular matrixes of both knees were improved in SW(T) and SW(F) compared to that of OP. Serum bone morphogenetic protein 2 (BMP2) in rats undergoing SW(T) or SW(F) was significantly improved compared to that in Sham and OP. The expressions of BMP2, BMP4, and SMAD family member 4 (Smad4) in addition to the Wnt family member 3A (Wnt3a) and Cyclin D1 signaling key factors were significantly induced in the cartilage of both knees by shockwave (SW). SW(T) presented the best efficacy to induce serum BMP2 to prevent bone loss from both lower limbs. Here, we display the protective effects of SW therapy to induce BMP2, BMP4, Smad4, Wnt3a, and Cyclin D1 signaling factors for cartilage loss in both knees of OVX rats.

Extracorporeal shockwave therapy (ESWT) and mesenchymal stem cells (MSCs) have been reported to have chondroprotective effects in knee osteoarthritis (OA). Here, we examined whether autologous adipose-derived mesenchymal stem cells (ADMSCs) and human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (WJMSCs) increased the efficacy of ESWT in knee OA, and compared the efficacy of the two. The treatment groups exhibited significant improvement of knee OA according to pathological analysis, micro-computed tomography (CT), and immunohistochemistry (IHC) staining. The ADMSCs and ESWT+ADMSCs groups exhibited increased trabecular thickness and bone volume as compared with the ESWT, WJMSCs, and ESWT+WJMSCs groups individually. According to the results of IHC staining, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) activity and caspase-3 were significantly reduced in the ADMSCs and ESWT+ADMSCs groups as compared with the WJMSCs and ESWT+WJMSC groups. In mechanistic factor analysis, the synergistic effect of ESWT+ADMSCs was observed as being greater than the efficacies of other treatments in terms of expressions of transforming growth factor (TGF)-β, runt-related transcription factor (RUNX)-2 and sex determining region Y-box (SOX)-9. The type II collagen was expressed at a higher level in the WJMSCs group than in the others. Furthermore, ESWT+ADMSCs reduced the expression of platelet-derived growth factor (PDGF)-BB and increased the expression of bone morphogenetic protein (BMP)-4. Therefore, we demonstrated that ESWT+ADMSCs had a synergistic effect greater than that of ESWT+WJMSCs for the treatment of early knee OA.

For recurrent patellar dislocation, reconstruction of the medial patellofemoral ligament (MPFL) with replacement autografts has often been performed but with only little data on the tensile properties of the MPFL to guide graft selection. With its complex anatomy and geometry, these properties are difficult to obtain. In this study, we showed how the orientation of the femur-MPFL-patella complex (FMPC) during uniaxial tensile testing can have a significant effect on its structural properties. Twenty two FMPCs were isolated from porcine stifle joints and randomly assigned to two groups of 11 each. For the first group, the specimens were loaded to failure with the patella oriented 30 degrees away from the direction of the applied load to mimic its orientation in situ, called natural orientation. In the second group, the patella was aligned in the direction of the tensile load, called non-natural orientation. The stiffness for the natural orientation group was 65 7 13 N/mm, 32% higher than that for the non-natural orientation group (50 7 17 N/mm; p < 0.05). The ultimate loads were 438 7 128 N and 386 7 136 N, respectively (p > 0.05). Ten out of 11 specimens in the natural orientation group failed at the femoral attachment (the narrowest portion of the MPFL) compared to 6 out of 11 in the non-natural orientation group. Our findings suggest that the specimen orientation that mimics the in-situ loading conditions of the MPFL should be used to obtain more representative data for the structural properties of the FMPC. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal shockwave therapy (ESWT) shows chondroprotective effect in osteoarthritis of the rat knees. However, the ideal number of ESWT is unknown. This study investigated the effects of different numbers of ESWT in osteoarthritis of the knee in rats. Methods: Forty-five male Sprague-Dawley rats were divided into five groups. Group I underwent sham arthrotomy without anterior cruciate ligament transection (ACLT) or medial meniscectomy (MM) and received no ESWT. Group II underwent ACLT + MM and received no ESWT. Group III underwent ACLT + MM, and received ESWT once a week for one treatment. Group IV underwent ACLT + MM and received ESWT twice a week for 2 treatments. Group V underwent ACLT + MM and received ESWT three times a week for 3 treatments. Each treatment consisted of 800 impulses of shockwave at 14 Kv to the medial tibia condyle. The evaluations included radiographs of the knee, histomorphological examination and immunohistochemical analysis at 12 weeks. Results: At 12 weeks, group II and V showed more radiographic arthritis than groups I, III and IV. On histomorphological examination, the Safranin O matrix staining in groups III and IV are significantly better than in groups II and V, and the Mankin scores in groups III and IV are less than groups II and V. Groups III and IV showed significant decreases of Mankin score and increase of Safranin O stain as compared to group I. Group V showed significant increases of Mankin score and a decrease of Safranin O stain as compared to group II. In articular cartilage, group II showed significant increase of MMP13 and decrease of collagen II as compared to group I. Groups III and IV showed significant decrease of MMP13 and increase of collagen II as compared to group I. Group V showed significant increase of MMP13 and decrease of collagen II as compared to group II. In subchondral bone, vWF, VEGF, BMP-2 and osteocalcin significantly decreased in groups II and V, but increased in groups III and IV relative to group I. Conclusions: ESWT shows a number of treatment related chondroproctective effect in osteoarthritis of the knee in rats. [ABSTRACT FROM AUTHOR]

Cocktail therapy consists of extracorporeal shock wave treatment (ESWT), hyperbaric oxygen therapy (HBO) and alendronate. We hypothesized that this combined therapy may produce better results than ESWT alone when treating hip necrosis. This prospective, randomized study evaluated the effectiveness of cocktail therapy in early hip necrosis, and then compared it to shock wave treatment alone. Sixty-three patients (98 hips) were randomly divided into two groups. Group A consisted of 28 patients (50 hips) who received cocktail therapy, and group B consisted of 35 patients (48 hips) who received only ESWT. Each affected hip was treated with 6,000 shocks of ESWT at 28 kV (equivalent to 0.62 mJ/mm2) in a single session. Cocktail patients also received HBO therapy performed in a multi-place chamber daily for 20 treatments, and they were administered 70 mg of alendronate orally per week for 1 year. The evaluations included clinical assessment, radiograph and MRI. After a minimum of 2-years of follow-up, the overall results showed 74% improved, 16% unchanged and 10% worsened in group A; and 79.2% improved, 10.4% unchanged and 10.4% worsened in group B ( P = 0.717). Total hip replacement (THR) was performed for 10% of group A and 10.4% of group B ( P = 0.946). MRI showed significant reduction in bone marrow edema and a trend of decrease in the size of the lesions in both groups, however, no difference was noted between the two groups. Cocktail therapy is effective for early hip necrosis, but the results are comparable to ESWT in short-term follow up. The joint effects of HBO and alendronate over EWST were not observed. Long-term results are needed to determine whether or not the synergistic effects of ESWT, HBO and alendronate over ESWT alone exist in early hip necrosis. [ABSTRACT FROM AUTHOR]

Ligaments and tendons are dense connective tissues that are important in transmitting forces and facilitate joint articulation in the musculoskeletal system. Their injury frequency is high especially for those that are functional important, like the anterior cruciate ligament (ACL) and medial collateral ligament (MCL) of the knee as well as the glenohumeral ligaments and the rotator cuff tendons of the shoulder. Because the healing responses are different in these ligaments and tendons after injury, the consequences and treatments are tissue- and site-specific. In this review, we will elaborate on the injuries of the knee ligaments as well as using functional tissue engineering (FTE) approaches to improve their healing. Specifically, the ACL of knee has limited capability to heal, and results of non-surgical management of its midsubstance rupture have been poor. Consequently, surgical reconstruction of the ACL is regularly performed to gain knee stability. However, the long-term results are not satisfactory besides the numerous complications accompanied with the surgeries. With the rapid development of FTE, there is a renewed interest in revisiting ACL healing. Approaches such as using growth factors, stem cells and scaffolds have been widely investigated. In this article, the biology of normal and healing ligaments is first reviewed, followed by a discussion on the issues related to the treatment of ACL injuries. Afterwards, current promising FTE methods are presented for the treatment of ligament injuries, including the use of growth factors, gene delivery, and cell therapy with a particular emphasis on the use of ECM bioscaffolds. The challenging areas are listed in the future direction that suggests where collection of energy could be placed in order to restore the injured ligaments and tendons structurally and functionally. [ABSTRACT FROM AUTHOR]

This study compared the functional outcomes of total hip (THA) in one and shockwave (ESWT) in the other in 17 patients with bilateral hip necrosis. In THA side, only one type of prosthesis was used and all components were press fixed. In ESWT side, each hip received 6,000 impulses of shockwave at 28 kv. The evaluations included pain score and Harris hip score, radiographs and MR images. The magnitudes of improvement in pain and function favored the ESWT side. Thirteen patients rated ESWT better than THA; four patients reported comparable results between THA and ESWT, and none graded THA better than ESWT. Better functional outcomes were observed after ESWT for early hip necrosis than THA for late cases in patients with bilateral hip disease. [ABSTRACT FROM AUTHOR]

The hypothesis of this study is that anterolateral (A-L) trans-tibia approach is better than anteromedial (A-M) technique in posterior cruciate ligament (PCL) reconstruction. The purpose of this prospective clinical study was to compare the functional outcomes of A-M and A-L trans-tibia approach in arthroscopic PCL reconstruction. Between 1999 and 2003, 55 patients (55 knees) with an average age of 30 ± 11 years (range 16–60 years) underwent arthroscopic single-bundle reconstruction for symptomatic isolated PCL tear. Patients were randomly divided into two groups with 28 patients (28 knees) undergoing A-M trans-tibia approach on odd-numbered days, and 27 patients (27 knees) with A-L trans-tibia approach on even-numbered days. Hamstring auto grafts were used in all cases. All patients received the same rehabilitation program postoperatively. The evaluation parameters included clinical assessment, functional outcome, ligament laxity and radiographic changes of the affected knee. Significant improvements in pain and function of the knee were observed at an average follow-up of 48 ± 15.9 months for A-M and 45.0 ± 13.7 months for A-L approach. However, the difference between the two techniques was statistically not significant. In IKDC for symptom-activity level, normal or nearly normal knees were noted in 68% of A-M and 67% of A-L approach, respectively, but no difference was noted between the two groups. In ligament laxity, approximately two-thirds of the knees showed normal posterior laxity with no difference between the two groups. Radiographs of the knee showed no discernible difference in the overall alignment and degenerative changes as well as the sizes of bone tunnel between the two groups. A-M and A-L trans-tibia arthroscopic PCL reconstructions produced comparable clinical results in short-term follow-up. Contrary to our initial hypothesis, the theoretical disadvantages of A-M technique including graft failure were not observed during the follow-up period. Long-term results are needed to confirm the adverse effects of A-M trans-tibia approach in PCL reconstruction. [ABSTRACT FROM AUTHOR]