Activation of SIRT1 promotes cartilage differentiation and reduces apoptosis of nucleus pulposus mesenchymal stem cells via the MCP1/CCR2 axis in subjects with intervertebral disc degeneration

Abstract

Intervertebral disc degeneration (Idd) is a condition involving disruption of the bone tissue distribution. Nucleus pulposus mesenchymal stem cells (NPMScs) and Sirtuin 1 (SIRT1) play important roles in bone diseases, therefore the aim of the present study was to evaluate the roles of SIRT1 and NPMScs in Idd. First, NPMScs were harvested from patients with Idd. Then, the NPMScs were treated with a SIRT activator, and monocyte chemoattractant protein 1 (McP1) and chemokine receptor 2 (ccR2) inhibitors. Indices related to NPMSc growth, proliferation, differentiation and apoptosis were measured. Subsequently, Idd rat models were established and were transfected with NPMScs overexpressing SIRT1. NPMSc apoptosis and cartilage differentiation were detected in the rat Idd model. SIRT1 expression was found to be decreased, and the expression of McP1 and ccR2 increased in NPMScs of patients with Idd. The upregulation of SIRT1 and the downregulation of the McP1/ccR2 axis promoted cartilage differentiation and reduced the number of apoptotic NPMScs. Furthermore, McP1 reversed the progression of the cartilage differentiation of NPMScs and the inhibition of NPMSc apoptosis induced by SIRT1 overexpression. Moreover, the transplantation of rat NPMScs overexpressing SIRT1 relieved Idd in rats. Therefore, SIRT1 overexpression improved cartilage differentiation and reduced the apoptosis of NPMScs by inactivating the McP1/ccR2 axis, thus attenuating Idd in rats.

Factors of Intervertebral Disc Rehydration after Percutaneous Endoscopic Lumbar Discectomy

“…Immune cells are widely involved in the occurrence and development of skeletal degenerative diseases 20 . Studies have shown that degraded nucleus pulposus and annulus brosus produce a large number of pro-in ammatory factors, including IL-1α, IL-β, TNF-α, and C-C motif chemokine ligand (CCL) 21 . These in ammatory chemokines further recruit immune cells to in ltrate the intervertebral disc, exacerbating the in ammatory response.…”

Genome Edited Sirt1-Overexpressing Human Mesenchymal Stem Cells Exhibit Therapeutic Effects in Treating Collagen-Induced Arthritis

“…To identify favorable factors driving anti-inflammation and regeneration, we examined one of the important factors, Sirt1, involved in cartilage repair. Recently, it has been reported that Sirt1 promotes chondrogenic differentiation and reduces MSC apoptosis (Ou et al, 2020). In addition, activation of Sirt1 inhibits inflammation and degradative processes in cartilage (Backesjo et al, 2009;Buhrmann et al, 2014).…”

Targeted screening of inflammatory mediators in spontaneous degenerative disc disease in dogs reveals an upregulation of the tumor necrosis superfamily

“…studies investigating naturally occurring canine 7,40 and (painful) human [41][42][43][44][45][46][47][48][49][50][51] IVD degeneration. Interestingly, several of these factors have been associated with MCs 52 and nerve sprouting within the IVD tissue resulting in discogenic pain.…”