Circulating microRNA let‑7e is decreased in knee osteoarthritis, accompanied by elevated apoptosis and reduced autophagy

Abstract

Knee osteoarthritis (KOA) is a major cause of leg disability in the elderly population. Recently, the expression levels of circulating microRNA (miRNA) let-7e have been reported to be significantly reduced in KOA. The aims of the present study were to assess the feasibility of let-7e as a serum marker for detecting KOA and to explore the underlying mechanisms of its involvement. Based on previous studies and bioinformatics analysis, let-7e may regulate apoptosis and autophagy of articular chondrocytes. A total of 10 patients with KOA and 10 patients with trauma without KOA were recruited to examine the levels of let-7e in peripheral blood. Subsequently, KOA rat models were established, and the levels of let-7e in the cartilage and serum were examined, the expression of apoptotic proteins and autophagy-related proteins in the cartilage were investigated, and apoptotic and autophagic activities of primary cultured chondrocytes were also detected. In patients with KOA, let-7e levels in the peripheral serum were significantly decreased compared with the control group, and this result was confirmed in the peripheral serum and cartilage of KOA rats. In addition, the expression levels of proteins involved in the apoptotic pathway were increased in the cartilage of KOA rats, and apoptotic activity was increased. The expression of autophagy-related proteins beclin 1 and microtubule associated protein 1 light chain 3 β (Lc3B) II/Lc3BI in the articular cartilage of KOA rats was lower compared with the controls, and autophagy was decreased. Si-Miao-San (SMS) treatment restored the expression of let-7e and reversed the changes in apoptosis and autophagy. Therefore, the present study provided additional evidence that circulating let-7e may be a potential serum biomarker for the diagnosis and treatment of KOA. Elevated apoptosis levels and decreased autophagy levels of cartilage tissue are involved in KOA, and treatment with SMS may reverse these effects.

Equine synovial fluid small non-coding RNA signatures in early osteoarthritis

“…Members of the let-7 family have often been described in studies involving OA; a large population-based study identified serum let-7e as a promising candidate to predict OA risk, independent of age, sex and body mass index [45]. A recent investigation supported this claim, providing further evidence of decreased expression of let-7e in serum of patients affected with knee OA [46]. The exact roles of miRNAs of the let-7 family remain unclear, but the evidence for their use as biomarkers for OA is growing.…”

The Role of Autophagy in Osteoarthritis

“…In recent years, the inhibition of chondrocytes apoptosis by autophagy activation has attracted much attention (Shapiro et al, 2014). Recent studies have shown that the level of autophagy in OA cartilage is reduced (Feng et al, 2020), and autophagy can protect chondrocytes from degradation (Caramés et al, 2012). With the progress of OA, mammalian target of rapamycin (mTOR), the main negative regulator of autophagy, is up-regulated and mediates the inhibition of autophagy signal transduction in articular cartilage, and the protective effect of autophagy on cartilage decreases, eventually promoting cartilage degeneration (Vasheghani et al, 2015).…”

Metformin Attenuates Monosodium-Iodoacetate-Induced Osteoarthritis via Regulation of Pain Mediators and the Autophagy–Lysosomal Pathway

“…Autophagy is an essential cellular and molecular mechanism that is important for maintaining cellular homeostasis [ 39 ], and it has been reported that autophagy is reduced in the cartilage of OA patients [ 40 ]. Recently Wang and colleagues reported the protective effects of metformin against osteoarthritis through the activation of autophagy [ 41 , 42 ].…”