Abstract:Osteoarthritis (OA) is a degenerative disease resulting from progressive joint destruction caused by many factors. Its pathogenesis is complex and has not been elucidated to date. Advanced glycation end products (AGEs) are a series of irreversible and stable macromolecular complexes formed by reducing sugar with protein, lipid, and nucleic acid through a non-enzymatic glycosylation reaction (Maillard reaction). They are an important indicator of the degree of ageing. Currently, it is considered that AGEs accum… Show more
“…Diabetes mellitus (DM, hyperglycemia) and OA interact at local and systemic levels. Local effects of ROS and AGEs were implicated in cartilage damage [74]. Studies included in the present review revealed that delphinidin, a potent antioxidant, and AGEs affect the viability of human chondrocyte cells via autophagy [10,20].…”
Background: Although osteoarthritis (OA) development is epidemiologically multifactorial, a primary underlying mechanism is still under debate. Understanding the pathophysiology of OA remains challenging. Recently, experts have focused on autophagy as a contributor to OA development. Method: To better understand the pathogenesis of OA, we survey the literature on the role of autophagy and the molecular mechanisms of OA development. To identify relevant studies, we used controlled vocabulary and free text keywords to search the MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and SCOPUS database. Thirty-one studies were included for data extraction and systematic review. Among these studies, twenty-five studies investigated the effects of autophagy in aging and OA chondrocytes, six studies examined the effects of autophagy in normal human chondrocytes, and only one study investigated the effects of mechanical stress-induced autophagy on the development of OA in normal chondrocytes. Results: The studies suggest that autophagy activation prevents OA by exerting cell-protective effects in normal human chondrocytes. However, in aging and osteoarthritis (OA) chondrocytes, the role of autophagy is intricate, as certain studies indicate that stimulating autophagy in these cells can have a cytotoxic effect, while others propose that it may have a protective (cytoprotective) effect against damage or degeneration. Conclusions: Mechanical stress-induced autophagy is also thought to be involved in the development of OA, but further research is required to identify the precise mechanism. Thus, autophagy contributions should be interpreted with caution in aging and the types of OA cartilage.
“…Diabetes mellitus (DM, hyperglycemia) and OA interact at local and systemic levels. Local effects of ROS and AGEs were implicated in cartilage damage [74]. Studies included in the present review revealed that delphinidin, a potent antioxidant, and AGEs affect the viability of human chondrocyte cells via autophagy [10,20].…”
Background: Although osteoarthritis (OA) development is epidemiologically multifactorial, a primary underlying mechanism is still under debate. Understanding the pathophysiology of OA remains challenging. Recently, experts have focused on autophagy as a contributor to OA development. Method: To better understand the pathogenesis of OA, we survey the literature on the role of autophagy and the molecular mechanisms of OA development. To identify relevant studies, we used controlled vocabulary and free text keywords to search the MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and SCOPUS database. Thirty-one studies were included for data extraction and systematic review. Among these studies, twenty-five studies investigated the effects of autophagy in aging and OA chondrocytes, six studies examined the effects of autophagy in normal human chondrocytes, and only one study investigated the effects of mechanical stress-induced autophagy on the development of OA in normal chondrocytes. Results: The studies suggest that autophagy activation prevents OA by exerting cell-protective effects in normal human chondrocytes. However, in aging and osteoarthritis (OA) chondrocytes, the role of autophagy is intricate, as certain studies indicate that stimulating autophagy in these cells can have a cytotoxic effect, while others propose that it may have a protective (cytoprotective) effect against damage or degeneration. Conclusions: Mechanical stress-induced autophagy is also thought to be involved in the development of OA, but further research is required to identify the precise mechanism. Thus, autophagy contributions should be interpreted with caution in aging and the types of OA cartilage.
“…These irreversible AGEs, formed through non-enzymatic glycation reactions (Maillard reaction), stand as crucial indicators of aging, implicated as a mechanistic basis for age-induced OA, highlighting their role in inducing and accelerating OA's pathological changes. AGEs' influence on chondrocyte behavior includes increased apoptosis rates, MMP13 expression, and inhibition of chondrocyte autophagy, mediated through intricate pathways involving phosphorylation of key proteins and modulation of signaling cascades [ 146 , 147 ]. Fig.…”
Section: Glycosylation and Glycation Abnormalities In Oamentioning
“…ACTR2A, activin receptor 2 A; ACTR2B, activin receptor 2B; ALK, activin-like kinase; TGFβRII, transforming growth factor β receptor type II; BMPR2, bone morphogenetic protein receptor type 2. cartilage, while the degradation of aggrecan renders the chondrocytes inelastic, further leading to the destruction of cartilage. 27,28 Biver et al 13 found that an increase in BMP levels in cartilage stimulated the excessive synthesis of chondrocyte matrix and MMP-13, which can promote tissue repair and stimulate cartilage degeneration to induce OA, respectively. Mechanical damage to joints can induce articular cartilage to express terminal hypertrophy markers such as MMP-13 and lead to the damage of collagen network, 29 therefore leading to OA.…”
Section: The Structure Of Articular Cartilage Under Physiological Con...mentioning
Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.
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