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.

Shockwave Therapy Modulates the Expression of BMP2 for Prevention of Bone and Cartilage Loss in the Lower Limbs of Postmenopausal Osteoporosis Rat Model.

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.

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.

Comparison efficacy of ESWT and Wharton's jelly mesenchymal stem cell in early osteoarthritis of rat knee.

Application of extracorporeal shockwave therapy (ESWT) to the subchondral bone of medial tibia condyle has shown chondroprotective effects of the knee with decreased cartilage degradation and improved subchondral bone remodeling in the osteoarthritis (OA) of rat knee. Recently, transplantation of ex vivo preparations of mesenchymal stem cells (MSCs) to animal or human joints with OA seems to induce therapeutically effective repair because of paracrine responses from host cells including progenitor cells residing within the synovium. This study compared ESWT, Wharton's jelly mesenchymal stem cells (WJMSCs) and combination of ESWT and WJMSCs therapies for early OA of the rat knee. The results showed ESWT, WJMSCs and combination of therapies significantly improved early OA knee based on analysis of pathological findings, micro-CT and immunohistochemistry (IHC) stain. The combined therapy group increased the bone volume (61.755 ± 1.537), and trabecular thickness (0.215 ± 0.014; P < 0.01) as well as reduced synovitis (1.8 ± 0.37) more than ESWT or WJMSCs individually. However, there were no significant difference in combined ESWT and WJMSCS as shown in the expressions of IGF-1 and TGF-ß1 and reduction of the TUNEL activity on OA knee. Furthermore, WJMSCs treatment significantly increased the expression of the type II collagen (22.62 ± 0.84; P < 0.001) when compared with ESWT (6.97 ± 0.54) and ESWT combined with WJMSCs (8.87 ± 0.31) in OA knee. In mechanistic factors analysis, the synergistic effect was observed by ESWT combined with WJMSCs in the expression of RUNX-2, SOX-9 and Collagen Xα1 on OA knee. Our results provided the innovative information of ESWT, and WJMSCs in the treatment of early osteoarthritis of the knee in rats.