Extracorporeal Shockwave Therapy Modulates the Expressions of Proinflammatory Cytokines IL33 and IL17A, and Their Receptors ST2 and IL17RA, within the Articular Cartilage in Early Avascular Necrosis of the Femoral Head in a Rat Model.

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 < 0.01) and the trabecular thickness (P < 0.001), while in contrast, the trabecular number and trabecular separation were not significantly different after treatment as compared with AVNFH. ESWT protected the articular cartilage in animal model of AVNFH. The levels of IL1-ß and IL33 were significantly induced in the AVNFH group (P < 0.001) as compared with Sham and ESWT groups and reduced in ESWT group (P < 0.001) as compared with AVNFH group. In addition, the expression of the receptor of IL33, ST2, was reduced in AVNFH and induced after ESWT (P < 0.001). The expression of IL17A was induced in the AVNFH group (P < 0.001) and reduced in the ESWT group (P < 0.001). Further, the expression of the receptor of IL17A, IL17RA, was reduced in the AVNFH group (P < 0.001) and improved to a normal level in the ESWT group as compared with Sham group (P < 0.001). Taken together, the results of the study indicated that ESWT modulated the expression of IL1-ß, pro-inflammatory cytokines IL33 and IL17A, and their receptors ST2 and IL17RA, to protect against loss of the extracellular matrix in the articular cartilage of early AVNFH.

Is coracoclavicular reconstruction necessary in hook plate fixation for acute unstable acromioclavicular dislocation?

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.

Shockwave Therapy Combined with Autologous Adipose-Derived Mesenchymal Stem Cells Is Better than with Human Umbilical Cord Wharton's Jelly-Derived Mesenchymal Stem Cells on Knee Osteoarthritis.

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)-ß, 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.

Identification of nuclear localization signal and nuclear export signal of VP1 from the chicken anemia virus and effects on VP2 shuttling in cells.

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.

Shockwave Targeting on Subchondral Bone Is More Suitable than Articular Cartilage for Knee Osteoarthritis.

Our study compared the effects of extracorporeal shockwave therapy (ESWT) on the subchondral bone and the articular cartilage in the treatment of early osteoarthritis (OA) of rat knee. The rats were divided into 5 groups which included Sham group, Meniscus group (ESWT applied on medial meniscus), OA group (arthrotomy and medial menisectomy (MMx) and anterior cruciate ligament transection (ACLT), T(M) group (arthrotomy and MMx and ACLT followed by ESWT on medial tibial subchondral bone) and Articular cartilage group (arthrotomy and MMx and ACLT followed by ESWT on medial articular cartilage). Evaluations included the pathological changes of the synovium, articular cartilage and subchondral bone, and compared with ESWT on the meniscus, medial tibial subchondral bone and articular cartilage. The ESWT (0.25 mJ/mm² and 800 impulses) did not cause any damages on the cartilage of the meniscus and the tissue of the joint when compared with Sham group. Among the treatment of osteoarthritic groups (OA, T(M) and Articular cartilage groups), T(M) group showed significant in pathological examination, micro-CT analysis, cartilage grading score and grading of synovium changes by compared with OA and Articular cartilage groups (P < 0.05) in the treatment of early OA knee. In immunohistochemical analysis, T(M) group significantly increased the expression of TGF-ß1 but reduced DMP-1, MMP-13 and ADAMTS-5 in the cartilage by compared with OA group and Articular cartilage group (P < 0.05). Our results showed that subchondral bone was an excellent target than articular cartilage for ESWT on early knee osteoarthritis.

Changes of articular cartilage and subchondral bone after extracorporeal shockwave therapy in osteoarthritis of the knee.

We assessed the pathological changes of articular cartilage and subchondral bone on different locations of the knee after extracorporeal shockwave therapy (ESWT) in early osteoarthritis (OA). Rat knees under OA model by anterior cruciate ligament transaction (ACLT) and medial meniscectomy (MM) to induce OA changes. Among ESWT groups, ESWT were applied to medial (M) femur (F) and tibia (T) condyles was better than medial tibia condyle, medial femur condyle as well as medial and lateral (L) tibia condyles in gross osteoarthritic areas (p<0.05), osteophyte formation and subchondral sclerotic bone (p<0.05). Using sectional cartilage area, modified Mankin scoring system as well as thickness of calcified and un-calcified cartilage analysis, the results showed that articular cartilage damage was ameliorated and T+F(M) group had the most protection as compared with other locations (p<0.05). Detectable cartilage surface damage and proteoglycan loss were measured and T+F(M) group showed the smallest lesion score among other groups (p<0.05). Micro-CT revealed significantly improved in subchondral bone repair in all ESWT groups compared to OA group (p<0.05). There were no significantly differences in bone remodeling after ESWT groups except F(M) group. In the immunohistochemical analysis, T+F(M) group significant reduced TUNEL activity, promoted cartilage proliferation by observation of PCNA marker and reduced vascular invasion through observation of CD31 marker for angiogenesis compared to OA group (P<0.001). Overall the data suggested that the order of the effective site of ESWT was T+F(M) ≧ T(M) > T(M+L) > F(M) in OA rat knees.

Extracorporeal Shockwave Therapy Enhances Expression of Pdia-3 Which Is a Key Factor of the 1α,25-Dihydroxyvitamin D 3 Rapid Membrane Signaling Pathway in Treatment of Early Osteoarthritis of the Knee.

The goal of our research was demonstrated that multiple molecules in microenvironments of the early osteoarthritis (OA) joint tissue may be actively responded to extracorporeal shockwave therapy (ESWT) treatment, which potentially regulated biological function of chondrocytes and synovial cells in early OA knee. We demonstrated that shockwave treatment induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which was a significant mediator of the 1α,25-Dihydroxyvitamin D 3 (1α,25(OH)2D3) rapid signaling pathway, using two-dimensional electrophoresis, histological analysis and quantitative polymerase chain reaction (qPCR). We observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of other group at 4, 8, and 12 weeks post-shockwave treatment in early OA rat knee model. The other factors of the rapid membrane signaling pathway, including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were examined and were found to be significantly increased at 2 weeks post-shockwave treatment by qPCR in early OA of the knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of OA joint tissue that could be actively responded to ESWT, which may potentially regulate the biological functions of chondrocytes and osteoblasts in the treatment of the early OA of the knee.

The use of demineralized bone matrix for anterior cruciate ligament reconstruction: a radiographic, histologic, and immunohistochemical study in rabbits.

Tendon-bone healing is crucial in success of anterior cruciate ligament (ACL) reconstruction surgery. Demineralized bone matrix (DBM) is a physiological component that has the inherent potential of bone regeneration. We hypothesized that the alternative bone substitute can affect the structural properties of tendon graft in tibial tunnel healing. Five 12-week-old New Zealand white rabbits in study group underwent unilateral ACL reconstructions plus the application of 0.5 cc DBM in the tibial tunnel. The assessment included radiological assessment and histologic and immunohistochemical analyses. Radiological examination revealed that DBM group had the least displacement of tendon in tibial tunnel (0.4 ± 0.12; P = 0.03). Histologic examination showed significantly better integration between tendon and bone in DBM group (77.62 ± 2.08; P = 0.001). On immunohistochemical analysis, the DBM group showed significantly higher expressions of bone morphogenetic protein-2 and vascular endothelial growth factor than control group (51.98 ± 3.02, 84.06 ± 1.86; P = 0.001, P < 0.001). DBM enhances the tendon-bone healing in ACL reconstruction. DBM has the potential use in ACL surgery.

Shockwave therapy improves anterior cruciate ligament reconstruction.

BACKGROUND: Shockwave was shown to enhance the healing of anterior cruciate ligament (ACL) reconstruction in rabbits. This study evaluated the effect of extracorporeal shockwave therapy (ESWT) on ACL reconstruction in human subjects. We hypothesized that ESWT may improve human ACL reconstruction. METHODS: Fifty-three patients were randomized into two groups with 26 patients in ESWT group and 27 patients in control group. The ESWT group underwent single-bundle hamstring autograft ACL reconstruction and received ESWT immediately after surgery. The control group underwent ACL surgery without ESWT. Both groups received the same rehabilitation postoperatively. The evaluations included Lysholm score, IKDC score and KT-1000, radiograph, bone mineral density, and magnetic resonance imaging. RESULTS: ESWT group showed significantly better Lysholm score than control group at 1 and 2 y postoperatively (P < 0.001 and 0.001, respectively). No significant difference was noted in IKDC score between the two groups (P = 0.080 and 0.076, respectively). The KT-1000 values were significantly better in ESWT group than control group at 2 y postoperatively (P = 0.027). The tibia tunnel on X-ray was significantly smaller in ESWT group compared with control group at 2 y (P = 0.018). The bone mineral density values showed no discernable difference between the two groups at 6 mo and 2 y (P = 0.522 and 0.984, respectively). On magnetic resonance imaging, ESWT group showed significant decrease in tibia tunnel enlargement at 6 mo and 2 y compared with the control group (P = 0.024 and <0.001, respectively). CONCLUSIONS: ESWT significantly improves the subjective Lysholm score and decreases the middle 1/3 tibia tunnel enlargement after single hamstring autograft ACL reconstruction.

Extracorporeal shockwave therapy shows a number of treatment related chondroprotective effect in osteoarthritis of the knee in rats.

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.

Graft failure versus graft fixation in ACL reconstruction: histological and immunohistochemical studies in rabbits.

The causes of graft failure after anterior cruciate ligament (ACL) reconstruction are multifactorial including the methods of graft fixation. The purpose of this study was to examine the ACL graft failure in three different methods of graft fixations including interference screw fixation, suture-post fixation and combined interference screw and suture-post fixation. We hypothesized that the fixation method after ACL reconstruction can affect the graft healing in tibial tunnel. Eighteen New Zealand white rabbits were categorized into three groups according to the method of fixation in unilateral ACL reconstruction with long digital extensor autograft. Histological examination demonstrated that the combined fixation and suture-post fixation groups showed significantly better integration between tendon and bone (P = 0.04). In immunohistochemical analysis, the combined fixation and suture-post fixation groups showed significantly higher BMP-2 and VEGF expressions than interference screw (P < 0.01). The tendon-bone healing after ACL reconstruction was affected by the method of graft fixation. Combined fixation with interference screw and suture-post reduced graft-tunnel micromotion and improved the graft healing in tibial tunnel.

Pipkin Type I and II femoral head fractures: internal fixation or excision?-from the hip arthroscopy perspective.

The treatment of patients with femoral head fractures with regard to fixation versus excision is controversial. This study aimed to compare the results of fixation and excision in hip arthroscopy-assisted surgery. This retrospective study included adult patients with femoral head fractures who were treated with hip arthroscopy surgery from March 2016 to April 2020, with a minimum follow-up of 24 months. The patients were divided into two groups: Group 1 (fixation group) and Group 2 (excision group). To compare the therapeutic effects between the two groups, clinical and radiographic outcomes, operative time, pain score, length of hospital stay after surgery and related complications were investigated. There were 13 (mean duration, 47.5 months; range, 24-72 months) and 8 (mean duration, 48.6 months; range, 26-74 months) patients in the fixation and excision groups, respectively. The excision group had better functional results than the fixation group in terms of the median modified Harris hip score (P = 0.009). No significant differences were observed in operative time, pain score or hospital stay after surgery between the two groups. Further, no osteonecrosis of the femoral head or traumatic arthritis occurred in either group. A piece of fracture fragment >2 cm can be considered for hip arthroscopy-assisted internal fixation, whereas the others can be removed. The excision group had better outcomes than the fixation group. Hence, hip arthroscopy-assisted internal fixation or excision of bony fragments led to satisfactory short-term clinical and radiological results for the treatment of Pipkin Type I and II femoral head fractures.

Extracorporeal shockwave therapy shows time-dependent chondroprotective effects in osteoarthritis of the knee in rats.

BACKGROUND: Recent studies reported that extracorporeal shockwave therapy (ESWT) has a chondroprotective effect on the initiation and regression of osteoarthritis of the knee in rats. However, the time course effects of ESWT in the osteoarthritic knee are not fully understood. The purpose of this study was to evaluate the effects of ESWT over time on osteoarthritis of the knee in rats. METHODS: We used 72 8-week-old male Sprague-Dawley rats with body weights ranging from 245 to 265 g. We randomly divided the rats into three groups, with 24 rats in each group. The control group received neither surgery nor ESWT. The anterior cruciate ligament transected (ACLT) group underwent anterior cruciate ligament transection but received no ESWT. The ACLT plus ESWT group underwent ACL transection and received ESWT at 1 wk after surgery. The animals were killed at 2, 4, 8, and 12 wk, 6 rats from each group at each time course. Evaluation parameters included Mankin score, Safranin O stain, and collagen II for the articular cartilage; and vascular endothelial growth factor (VEGF), bone morphogenetic-2 (BMP-2), and osteocalcin for the subchondral bone using histopathological examination and immunohistochemical analysis. RESULTS: The ACLT group showed significant increases in Mankin score and Safranin O stain, and a decrease in collagen II in the articular cartilage, and significant decreases in VEGF, BMP-2, and osteocalcin in the subchondral bone compared with the control (P < .05). The ACLT + ESWT group showed significant decreases in Mankin score and Safranin O stain and an increase in collagen II in the articular cartilage, and significant increases in VEGF, BMP-2, and osteocalcin in the subchondral bone compared with the control group. The changes in the ACLT + ESWT group appeared to correlate with the time courses of treatment; the most beneficial effects were noticed 4 weeks after ESWT. CONCLUSION: Extracorporeal shockwave therapy is effective in preventing osteoarthritis of the knee in rats. The beneficial effects of ESWT appear to be time-dependent beginning at 4 weeks after treatment.

Effect of three clinical therapies on cytokines modulation in the hip articular cartilage and bone improvement in rat early osteonecrosis of the femoral head.

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.

Treatment of displaced fractures of the patella: Tension band wiring technique with the one-end or both-ends K-wire bending fixation method.

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.

Adipose-Derived Mesenchymal Stem Cells-Conditioned Medium Modulates the Expression of Inflammation Induced Bone Morphogenetic Protein-2, -5 and -6 as Well as Compared with Shockwave Therapy on Rat Knee Osteoarthritis.

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 1ß, 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.

Autologous Adipose-Derived Mesenchymal Stem Cells Combined with Shockwave Therapy Synergistically Ameliorates the Osteoarthritic Pathological Factors in Knee Joint.

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.

pCMV-BMP-2-transfected cell-mediated gene therapy in anterior cruciate ligament reconstruction in rabbits.

PURPOSE: This study investigated the effect of plasmid cytomegalovirus (pCMV)-bone morphogenetic protein 2 (BMP-2) gene therapy on the healing of the tendon-bone interface after anterior cruciate ligament (ACL) reconstruction in rabbits. METHODS: The pCMV-BMP-2 was synthesized from full-length human BMP-2 complementary deoxyribonucleic acid, followed by cloning into pCMV Script vector (Clontech Laboratories, Inc., San Jose, CA), and was delivered by a xenogeneic (rat kidney) cell line. The ACL was reconstructed by the transfer of extensor digital tendon in the proximal tibia. In the study group the pCMV-BMP-2 gene-transfected normal rat kidney cells mixed with calcium alginate gel were placed at the tendon-bone interface, whereas no pCMV-BMP-2 was used in the control group. The evaluations included radiography, bone mineral density, magnetic resonance imaging, biomechanical study, histologic examination, and immunohistochemical analysis. RESULTS: Bone mineral density showed no significant difference between the groups (P > .05). Magnetic resonance imaging showed significantly better contact between tendon and bone in the study group compared with the control group (P < .0001). In the biomechanical study, significantly higher failure load and maximal graft tension were noted in the study group compared with the control group (P = .034). The modes of graft failure were rupture of the tendon proper in 78% and graft pullout from the bone tunnel in 22% of specimens in the study group versus graft rupture in 22% and graft pullout in 78% in the control group (P = .018). On histologic examination, the study group showed significantly better integration between tendon and bone, as well as more bone tissue around the tendon graft, than the control group (P = .0004). On immunohistochemical analysis, the study group showed significantly higher expressions of von Willebrand factor, vascular endothelial growth factor, proliferation cell nuclear antigen, and BMP-2 than the control group (P < .05). CONCLUSIONS: The pCMV-BMP-2 gene therapy significantly improved the healing of tendon to bone and promoted angiogenesis and osteogenesis at the tendon-bone interface after ACL reconstruction in the rabbit model. CLINICAL RELEVANCE: Application of pCMV-BMP-2 gene therapy may be an effective adjunct therapy in ACL reconstruction.

Cocktail therapy for femoral head necrosis of the hip.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Treatment of type IV Pipkin fracture in patients with a high BMI via hip arthroscopy-assisted surgery: a case report.

Pipkin type IV femoral head (FH) fracture-dislocations are usually treated via open surgery. There are many surgical approaches for the treatment of this difficult fracture depending on the fracture pattern. Obesity presents another challenging problem in surgical treatment and sometimes leads to a poorer outcome. We discuss herein a patient of a high body mass index (BMI) with a Pipkin type IV FH fracture who underwent open reduction internal fixation (ORIF) of anacetabular fracture with reconstruction plates and hip arthroscopy-assisted fixation of the FH fracture with two Herbert screws via the posterior approach. The intra-articular osteochondral loose bodies were excised by hip arthroscopy simultaneously. The joint congruency and screw positions were checked during surgery by arthroscopy. After 6 months, clinical and computed tomography (CT) follow-ups showed excellent results. The patient of a high BMI recovered immediately and had a satisfactory short-term outcome after hip arthroscopy-assisted surgery. We concluded that hip arthroscopy-assisted surgery is a viable option for the treatment of Pipkin type IV FH fracture-dislocations.