Integrin-β1 regulates chondrocyte proliferation and apoptosis through the upregulation of GIT1 expression

Abstract

Chondrocytes play a critical role in the repair process of osteoarthritis, which is also known as degenerative arthritis. Integrins, as the key family of cell surface receptors, are responsible for the regulation of chondrocyte proliferation, differentiation, survival and apoptosis through the recruitment and activation of downstream adaptor proteins. Moreover, G-protein-coupled receptor kinase interacting protein-1 (GIT1) exerts its effects on cell proliferation and migration through interaction with various cytokines. It has been previously suggested that GIT1 acts as a vital protein downstream of the integrin-mediated pathway. In the present study, we investigated the effects of integrin-β1 on cell proliferation and apoptosis, as well as the underlying mechanisms in chondrocytes in vitro. Following transfection with a vector expressing integrin-β1, our results revealed that the overexpression of integrin-β1 enhanced GIT1 expression, whereas the knockdown of integrin-β1 by siRNA suppressed GIT1 expression. However, no significant effect was observed on integrin-β1 expression following the enforced overexpression of GIT1, which suggests that GIT1 is localized downstream of integrin-β1. In other words, integrin-β1 regulates the expression of GIT1. Furthermore, this study demonstrated that integrin-β1 and GIT1 increased the expression levels of aggrecan and type II collagen, thus promoting chondrocyte proliferation; however, they inhibited chondrocyte apoptosis. Taken together, our data demonstrate that integrin-β1 plays a vital role in chondrocyte proliferation, differentiation and apoptosis. GIT1 exerts effects similar to those of integrin-β1 and is a downstream target of integrin-β1.

MSC-derived exosomes promote proliferation and inhibit apoptosis of chondrocytes via lncRNA-KLF3-AS1/miR-206/GIT1 axis in osteoarthritis

“…A recent study [11] demonstrated that miR-206 overexpression significantly inhibited the proliferation, promoted chondrocyte apoptosis, dramatically decreased Col2a1 and aggrecan, and increased Runx2 and MMP-13 [11], indicating the involvement of miR-206 in cartilage degradation in OA. Furthermore, GIT1 has been shown to promote chondrocytes proliferation and inhibit chondrocytes apoptosis [12][13][14]. In the current study, we verified not only the direct binding between KLF3-AS1 and miR-206, but also 3ʹUTR of GIT1 and miR-206.…”

“…Extensive research has shown that G-proteincoupled receptor kinase interacting protein-1 (GIT1) promotes chondrocytes proliferation and inhibits chondrocytes apoptosis [12]. Zhao et al [13] stated that platelet-derived growth factor (PDGF) promotes chondrocyte proliferation but suppresses chondrocyte apoptosis via upregulating GIT1 expression.…”

Exosomal long noncoding RNAs in aging and age‐related diseases

“…Further studies showed that lncRNA KLF3 Antisense RNA 1 (KLF3‐AS1) in MSC‐Exos promoted the G‐protein‐coupled receptor kinase interacting protein‐1 (GIT1) expression through a miRNA‐206 sponge effect and alleviated the IL‐1β‐induced chondrocyte apoptosis and inhibition of proliferation. In addition, GIT1 promoted the chondrocyte proliferation and inhibited the chondrocyte apoptosis by increasing the aggrecan and Type II collagen expression . These data suggest that MSC‐Exos can improve OA by transferring lncRNAs to chondrocytes to regulate gene expression related to chondrocyte proliferation and can be used as a potential therapy for OA.…”

Periodic Mechanical Stress Stimulates GIT1-Dependent Mitogenic Signals in Rat Chondrocytes Through ERK1/2 Activity

“…Meantime, based on our present and previous results, periodic mechanical stress-activated GIT1 and Tyr 397 signals may act in parallel in this setting. Recently, GIT1 was viewed as an important integrin-associated kinase that receives and transmits various integrin-initiated intracellular biochemical signals [16,41,42]. The activation of GIT1 by integrin has been reported to be a signaling transduction mechanism.…”