Extracorporeal shock wave technology transmitted physical energy through acoustic wave under water generated by high voltage electrode. In contrast to lithotripsy by urologist, the orthopaedic shockwave is used to stimulate tissue regeneration and tissue repair. The application of shock wave therapy have successful treated certain musculoskeletal disorders including calcified tendinitis of shoulder, lateral epicondylitis, plantar fasciitis and nonunion of long bone fracture. Recently robust extrapolation of molecular mechanism of shock wave widespread extended the clinical usage including hip osteonecrosis, osteochondrtis dissecan, non-calcified tendinitis of shoulder, patellar tendinitis and osteoarthritis. Our previous researches established the fundamental molecular basis that shock wave triggers biological responses that stimulate the release of angiogenic factors such as endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) to induce neo-angiogenesis and tissue regeneration. Moreover, the promotion of bone morphogenetic protein (BMPs) by shock wave helps the bone repair. The discovered molecular mechanisms were universally recognized by the world experts. Furthermore, the proposed working mechanisms have expanded the use of shock wave to include other disease such as diabetic foot ulcer and ischemic heart disease. Osteoarthritis (OA), one of the most common causes of musculoskeletal disability, and is one of the leading causes of total knee arthroplasty in developed countries. Reportedly, increased bone turnover in subchondral bone associated with OA development and changes of bone mineral density correlated the progression of hip OA. However, the relationship between the subchondral bone changes and the initiation and progression of OA is still debated. The results of our recent study demonstrated that ESWT prevents the initiation of OA changes of the knee when it is applied earlier. We hypothesized that ESWT may retard or regress or reverse the process of osteoarthritic changes when it is utilized in knees with established OA. A growing body of evidence has demonstrated ESWT promoted tissue repair in various tissue and initiated biological responses. Our preliminary proteomic data revealed abundant significant proteins that warrant further characterization. These proteins of interest were reported to participate in the cellular response to stress, calcium homeostasis, chemotaxis and lipid oxidative stress in several tissue types under pathological contexts. Therefore, we hypothesize that multiple molecules in joint tissue microenviorments may be actively responded to ESWT treatment, which potentially regulate biological function of chondrocytes and synovial cells in OA knee. Delineating the active responsive molecules underlying ESWT-regulated biological responses using comparative proteomic technique helps the construct of molecular mechanism of alleviation of OA. Based on these translational experimental data, we could further explore a new regime with good potential for rescuing OA knee joint injury. Moreover, osteonecrosis of the femoral head (ONFH) is a skeletal disorder characterized by ischemic deterioration, bone marrow edema and eventually femoral head collapse. Several surgical, pharmaceutical and non-invasive biophysical modalities, including core decompression, bisphosphonate administration, extracorporeal shockwave therapy and hyperbaric oxygen, have been employed to alleviate this joint disorder. The shock wave therapy promoted the regression of early osteonecrotic femoral head. The molecular mechanisms underlying ESWT promoting biological response is not well defined. Therefore, we hypothesize that bioactive signaling that responded to ESWT, which potentially regulated the function of bone cell in osteonecrotic femoral head. In conjunction with hyperbaric oxygen therapy, ESWT promoted bone tissue repair through particular bioactive signaling delineated the new molecular basis of therapeutic potentials. The primary purpose of this co-ordinate study w1as first to investigate the effects of ESWT in the regression or reversal of OA changes of the knee in rats and the molecular mechanism under Dkk1-active response molecules. The secondary purpose was to explore the ESWT-promoted bioactive signaling in alleviation of osteonecrosis of femoral head and compared the adjunctive HBO therapy on the effect of osteonegesis in osteonecrosis of femoral head.
Specific aims of this study as the following:
(1)We plan to extend our sample size to verify the effect of ESWT on the regression or reversal of OA development.
(2)We will explore ESWT strategy for preventing joint tissue damage in OA knee and employ proteomic technology to screen the differential proteins that active respond to ESWT.
(3)We want to testify the combination of HBO and ESWT therapy superior to either treatment modality alone in enhancing angiogenesis and osteogenesis.
(4)We want to elucidate the molecular mechanism of HBO and ESWT therapy alleviated ONFH.