LncRNA SNHG1 overexpression alleviates osteoarthritis via activating PI3K/Akt signal pathway and suppressing autophagy.

ABSTRACT

We hereby intend to further explore and confirm the underlying mechanism of Small nucleolar RNA Host Gene 1 (SNHG1) in osteoarthritis (OA). For in vitro assays, OA was induced in primary chondrocytes with interleukin-1ß (IL-1ß) treatment; while for in vivo tests, OA model was established in mice using the destabilization of the medial meniscus (DMM) method. Cell viability and apoptosis were assessed with MTT and flow cytometry assays, respectively. Cartilage tissue was stained by Safranin-O/Fast Green Staining. The mRNA and protein levels were separately determined via quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. SNHG1 overexpression promoted the viability yet inhibited the apoptosis of chondrocytes injured by IL-1ß. Moreover, the overexpression of SNHG1 promoted B-cell lymphoma-2 (Bcl-2) expression and activated phosphoinositol-3 kinase (PI3K)/protein kinase B (Akt) pathway but suppressed the process of autophagy, which led to down-regulation of light chain 3 (LC3)-II/I level and up-regulation of P62 level. However, rapamycin (RAPA, an autophagy activator) and LY294002 (a PI3K inhibitor) reversed the effects of SNHG1 overexpression on the viability and apoptosis of chondrocytes as well as on the proteins related to PI3K/Akt pathway and autophagy. In OA-modeled mice, SNHG1 overexpression prevented the loss of chondrocytes via the activation of PI3K/Akt pathway and the suppression of autophagy. SNHG1 overexpression might inhibit the apoptosis of chondrocytes by promoting PI3K/Akt pathway and inhibiting autophagy.