MicroRNAs and long non-coding RNAs in cartilage homeostasis and osteoarthritis

During the last decade, osteoarthritis (OA) has become one of the most prevalent musculoskeletal diseases worldwide. OA is characterized by progressive loss of articular cartilage, abnormal remodeling of subchondral bone, hyperplasia of synovial cells, and growth of osteophytes, which lead to chronic pain and disability. The pathological mechanisms underlying OA initiation and progression are still poorly understood. Non-coding RNAs (ncRNAs) constitute a large portion of the transcriptome that do not encode proteins but function in numerous biological processes. Cumulating evidence has revealed a strong association between the changes in expression levels of ncRNA and the disease progression of OA. Moreover, loss- and gain-of-function studies utilizing transgenic animal models have demonstrated that ncRNAs exert vital functions in regulating cartilage homeostasis, degeneration, and regeneration, and changes in ncRNA expression can promote or decelerate the progression of OA through distinct molecular mechanisms. Recent studies highlighted the potential of ncRNAs to serve as diagnostic biomarkers, prognostic indicators, and therapeutic targets for OA. MiRNAs and lncRNAs are two major classes of ncRNAs that have been the most widely studied in cartilage tissues. In this review, we focused on miRNAs and lncRNAs and provided a comprehensive understanding of their functional roles as well as molecular mechanisms in cartilage homeostasis and OA pathogenesis

The protective effects of bexarotene against advanced glycation end-product (AGE)-induced degradation of articular extracellular matrix (ECM)

AbstractOsteoarthritis (OA) is a common debilitating disease primarily characterised by excessive loss of the articular ECM, which is composed of up to 95% type II collagen. Among the factors that contribute to the pathogenesis of OA, the natural process of aging is regarded as the most significant risk factor. AGEs, which are extremely resilient to degradation, are produced in the body naturally as a result of the Maillard process of nonenzymatic glycation and are also introduced through diet and tobacco smoke. AGEs have a high affinity for collagen and therefore accumulate in joint tissues, where they induce increased expression of proinflammatory cytokines, chemokines, and degradative enzymes. Additionally, AGEs induce oxidative stress, which further exacerbates the degradative process. Type II collagen is targeted for degradation by matrix metalloproteinases (MMPs), particularly MMP-3 and MMP-13, and AGEs have been shown to trigger increased expression of these MMPs. The role of retinoid and rexinoid receptors as specific treatment targets has been receiving increasing attention. Bexarotene is a retinoid X receptor (RXR) agonist used for the treatment of T-cell lymphoma and other cancers which has displayed a favourable safety profile. Here, we examined the roles of RXR agonism using bexarotene on AGE-induced markers of OA, including oxidative stress, inflammatory response, and MMP-mediated degradation of type II collagen. Furthermore, we demonstrate that bexarotene inhibited phosphorylation of IκBα, thereby suppressing activation of the proinflammatory NF-κB cellular signalling pathway. These findings present a basis for selective targeting of RXR by bexarotene as a potential treatment of OA induced by AGEs

Integrating network pharmacology and experimental verification strategies to reveal the active ingredients and molecular mechanism of Tenghuang Jiangu Capsule against osteoporosis

Tenghuang Jiangu Capsule (THJGC) is a Chinese herbal formula used for the treatment of osteoporosis and osteoarthritis in China, but its mechanism for treating osteoporosis is not clear. The aim of this study was to investigate the therapeutic effect of THJGC on osteoporosis and its intrinsic mechanism through network pharmacology and experimental validation. Drugs and potential targets were obtained from several reliable databases through network pharmacology, and these targets were integrated and analyzed using bioinformatics and molecular docking strategies. Quercetin, lignans and kaempferol were identified as key components, and the key targets included Akt1, MAPKs, and CASP3. Subsequently, UPLC-MS/MS analysis confirmed the presence of components in THJGC for the treatment of osteoporosis. In addition, using ex vivo and in vivo models, it was confirmed that THJGC inhibited H2O2-induced ROS generation and apoptosis, and reduced OVX-induced bone loss in a mouse model of osteoporosis. Our data suggest that THJGC has antioxidant, bone formation-promoting, bone resorption-inhibiting, and MC3T3-E1 apoptosis-reducing effects, and thus has anti-osteoporotic properties. In conclusion, it may be a promising pharmacologic adjuvant treatment for osteoporosis