Shan-Ling Hsu

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.

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

BackgroundExtracorporeal 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.MethodsForty-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.ResultsAt 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.ConclusionsESWT shows a number of treatment related chondroproctective effect in osteoarthritis of the knee in rats.

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.