Acupotomy Contributes to Suppressing Subchondral Bone Resorption in KOA Rabbits by Regulating the OPG/RANKL Signaling Pathway.

Subchondral bone lesions, as the crucial inducement for accelerating cartilage degeneration, have been considered as the initiating factor and the potential therapeutic target of knee osteoarthritis (KOA). Acupotomy, the biomechanical therapy guided by traditional Chinese meridians theory, alleviates cartilage deterioration by correcting abnormal mechanics. Whether this mechanical effect of acupotomy inhibits KOA subchondral bone lesions is indistinct. This study aimed to investigate the effects of acupotomy on inhibiting subchondral bone resorption and to define the possible mechanism in immobilization-induced KOA rabbits. After KOA modeling, 8 groups of rabbits (4w/6w acupotomy, 4w/6w electroacupuncture, 4w/6w model, and 4w/6w control groups) received the indicated intervention for 3 weeks. Histological and bone histomorphometry analyses revealed that acupotomy prevented both cartilage surface erosion and subchondral bone loss. Further, acupotomy suppressed osteoclast activity and enhanced osteoblast activity in KOA subchondral bone, showing a significantly decreased expression of tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinases-9 (MMP-9), and cathepsin K (Ctsk) and a significantly increased expression of osteocalcin (OCN); this regulation may be mediated by blocking the decrease in osteoprotegerin (OPG) and the increase in NF-κB receptor activated protein ligand (RANKL). These findings indicated that acupotomy inhibited osteoclast activity and promoted osteoblast activity to ameliorate hyperactive subchondral bone resorption and cartilage degeneration in immobilization-induced KOA rabbits, which may be mediated by the OPG/RANKL signaling pathway. Taken together, our results indicate that acupotomy may have therapeutic potential in KOA by restoring the balance between bone formation and bone resorption to attenuate subchondral bone lesions.

Chondroprotective Effects of Combination Therapy of Acupotomy and Human Adipose Mesenchymal Stem Cells in Knee Osteoarthritis Rabbits via the GSK3ß-Cyclin D1-CDK4/CDK6 Signaling Pathway.

Adipose-derived stem cells (ASCs) are highly chondrogenic and can be used to treat knee osteoarthritis (KOA) by alleviating cartilage defects. Acupotomy, a biomechanical therapy guided by traditional Chinese medicine theory, alleviates cartilage degradation and is widely used in the clinic to treat KOA by correcting abnormal mechanics. However, whether combining acupotomy with ASCs will reverse cartilage degeneration by promoting chondrocyte proliferation in KOA rabbits is unknown. The present study aimed to investigate the effects of combination therapy of acupotomy and ASCs on chondrocyte proliferation and to determine the underlying mechanism in rabbits with KOA induced by knee joint immobilization for 6 weeks. After KOA modeling, five groups of rabbits (acupotomy, ASCs, acupotomy + ASCs, model and control groups) received the indicated intervention for 4 weeks. The combination therapy significantly restored the KOA-induced decrease in passive range of motion (PROM) in the knee joint and reduced the elevated serum level of cartilage oligomeric matrix protein (COMP), a marker for cartilage degeneration. Furthermore, magnetic resonance imaging (MRI) and scanning electron microscopy (SEM) images showed that the combination therapy inhibited cartilage injury. The combination therapy also significantly blocked increases in the mRNA and protein expression of glycogen synthase kinase-3ß (GSK3ß) and decreases in the mRNA and protein expression of cyclin D1/CDK4 and cyclin D1/CDK6 in cartilage. These findings indicated that the combination therapy mitigated knee joint immobility, promoted chondrocyte proliferation and alleviated cartilage degeneration in KOA rabbits, and these effects may be mediated by specifically regulating the GSK3ß-cyclin D1-CDK4/CDK6 pathway.

Electroacupuncture alleviates cartilage degradation: Improvement in cartilage biomechanics via pain relief and potentiation of muscle function in a rabbit model of knee osteoarthritis.

Knee osteoarthritis (KOA) is a chronic degenerative joint disorder characterized by loss of articular cartilage and progressive deterioration, leading to pain and functional limitation. Abnormal biomechanics play a core role in the onset and development of KOA. The aim of this study was to explore whether electroacupuncture (EA) may relieve pain and adjust the biomechanical properties of the extensor-flexor muscles to improve abnormal joint loading, thus alleviating the degradation of cartilage in a rabbit model of KOA. Firstly, a KOA model was induced by immobilization for 6 weeks. Then, different interventions (EA and celecoxib) were applied for 4 weeks. The levels of pain and disability were assessed using the Lequesne MG index. Muscle function, including function of the rectus femoris and biceps femoris, was tested through hematoxylin-eosin staining (HE staining) and use of a microforce tension-torsion instrument. The cartilage was tested using nanoindentation, Safranin O-Fast Green staining, confocal laser scanning microscopy (immunofluorescence), immunohistochemistry and the enzyme-linked immunosorbent assay (ELISA). Finally, we found that EA and celecoxib resulted in lower behavioral and pain scores than the model group. In addition, it improved the function of muscles. Furthermore, those treatments alleviated the rate of cartilage degradation, manifested as increased loss factor without statistical difference and a significant reduction in the Mankin score. This promoted the metabolism of type II collagen in the cartilage layer and drastically reduced the expression of CTX-II in the synovial fluid and peripheral serum. Concisely, EA promotes pain limitation and ameliorates muscular atrophy-induced inappropriate biomechanical loading on the articular cartilage through pain relief and potentiation of muscle function, thus improving cartilage viscoelasticity, as demonstrated by the retarded degradation of type II collagen in our KOA model.

A comparison of the effects of electroacupuncture vs transcutaneous electrical nerve stimulation for pain control in knee osteoarthritis: A protocol for network meta-analysis of randomized controlled trials.

BACKGROUND: Knee osteoarthritis (KOA), the most common type of osteoarthritis, is a chronic degenerative joint disease accompanied by pain and functional limitation for the elderly. The 2 nonpharmacologic approaches, electroacupuncture (EA) and transcutaneous electrical nerve stimulation (TENS), are considered beneficial in relieving KOA pain, however, the current conclusions are controversial. Furthermore, no direct or indirect meta-analyses between EA and TENS have been reported for the pain relief of KOA patients. METHODS: PubMed, EMBASE, Cochrane library, Web of Science, CNKI, VIP, Wan Fang will be systematically searched their inception to May 2018. Randomized controlled trials that compared the effect of EA and TENS on pain control in knee osteoarthritis will be included. The primary outcome was the knee pain levels, and secondary outcome was the comprehensive indicators. Risk of bias assessment of the included studies will be performed according to the Cochrane risk of bias tool. The pairwise and network meta-analysis will be performed by STATA 14.0 software. RESULTS: This study is ongoing and will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide comprehensive evidence on the effects of EA and TENS for pain control in knee osteoarthritis. PROSPERO REGISTRATION NUMBER: CRD42018091826.