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This comprehensive approach addresses multiple aspects of tissue regeneration and aging

Off-label use means the medication is being used in a way that is different from that described in the license

Because of the close relationship between risk factors in human metabolism and the expression of GLP-1R in the musculoskeletal system, GLP-1RAs may have great potential in the treatment of many diseases of the musculoskeletal system.15,272 GLP-1RAs and joint disordersGLP-1RAs in OA GLP-1R expression was detected via immunohistochemistry in articular chondrocytes from both normal and osteoarthritic individuals.273 The primary outcome of GLP-1R expression involves suppressing the release of cytokines into the synovial fluid, leading to a reduction in inflammation.274,275 This, in turn, diminishes additional downstream effects, including oxidative stress, the secretion of pro-degradative substances, modifications to cell phenotype (hypertrophy, M1/M2 macrophage phenotype, fibrosis), and damage or deterioration of joint cells (apoptosis, senescence).15,276 The activation of GLP-1R is linked to decreased NF-B pathway activity Treatment with GLP-1RAs can effectively mitigate chondrocyte apoptosis caused by endoplasmic reticulum stress and alleviate the associated inflammatory response.277,278,279,280 This effect is accomplished through the inhibition of JNK, NF-B, and other relevant signaling pathways.273 Moreover, GLP-1RAs could decelerate the progression of OA and mitigate pathological damage in a rat OA model.273 In addition, in a rat model of inflammatory OA induced by monoiodoacetic acid (MIA), researchers have shown that the activation of GLP-1R triggers the PKA/CREB signaling pathway, leading to a reduction in cartilage inflammation.281 Inflammation in OA is closely related to the activation of macrophages.282,283 These cells accumulate in the synovial membrane and subchondral bone, releasing pro-inflammatory cytokines such as TNF-, IL-1, and IL-6, which promote the degradation of joint cartilage and the inflammatory response.284,285,286 Macrophages express GLP-1Rs, which are involved in regulating their inflammatory responses