Abstract
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.
Highlights
Osteoarthritis (OA) is a well-known cartilage disease that involves degradation and loss of articular cartilage [1]
We demonstrated that extracorporeal shockwave therapy (ESWT) had a synergistic effect with autologous adipose-derived mesenchymal stem cells (ADMSCs) on early knee OA
We found that ESWT combined with autologous ADMSCs was better than ESWT with xenografted Wharton’s jelly-derived mesenchymal stem cells (WJMSCs) in terms of joint repair in knee OA
Summary
Osteoarthritis (OA) is a well-known cartilage disease that involves degradation and loss of articular cartilage [1]. Previous studies have demonstrated that early (2-week OA) and late (12-week OA) application of extracorporeal shockwave therapy (ESWT) to the subchondral bone in the medial tibia condyle prior to development of OA changes exerted chondroprotective effects on the knee, with decreased cartilage degradation and improved subchondral bone remodeling, in a knee OA model in rats [3,4,5]. The results illustrated that ESWT can prevent or ameliorate the initiation or progressive change of OA in the knee when applied sooner. Some studies have shown that ESWT promotes neovascularization (von Willebrand factor, vWF; vascular endothelial growth factor, VEGF; endothelial nitric oxide synthase, eNOS; and proliferating cell nuclear antigen, PCNA), bone-healing (bone morphogenetic protein-2, osteocalcin, alkaline phosphatase, dickkopf-related protein-1, and insulin-like growth factor), anti-inflammatory effects (Serum levels of soluble intercellular adhesion molecule and soluble vasccular cell adhesion molecule), and wound-healing (Wnt, Wnt5a, and beta-catenin) [10,11,12,13,14]. ESWT exhibits biological effects in terms of repairing bone by stimulation of expressions of eNOS, PCNA, VEGF, bone morphogenetic protein-2, and osteocalcin [3,11,15]
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