The role of SIRT1 in BMP2-induced chondrogenic differentiation and cartilage maintenance under oxidative stress

Abstract

Articular cartilage defects are common in the clinic but difficult to treat. Exploring the chondrogenic molecular mechanisms of mesenchymal stem cells (MSCs) is of great theoretical interest and industrial significance. Bone morphogenetic protein 2 (BMP2) is a key factor that induces cartilage differentiation and can induce stem cell chondrogenic differentiation. However, the oxidative stress in the microenvironment during cartilage injury and degeneration inhibits cartilage regeneration and homeostasis. Silent mating type information regulator 2 homolog-1 (SIRT1) is an important histone deacetylase that regulates proliferation, differentiation, aging, and inflammation processes; moreover, it is an essential factor for chondrogenesis. The specific mechanism of SIRT1 in cartilage differentiation and homeostasis is still unclear. First, we investigated whether SIRT1 could coordinate BMP2-induced chondrogenic differentiation. Second, we investigated the protective effect of SIRT1 on BMP2-induced MSCs under oxidative stress. The results showed that SIRT1 could promote BMP2-induced chondrogenic differentiation of MSCs, and reduce the apoptosis and decomposition of extracellular matrix under oxidative stress. In summary, these results suggested that SIRT1 plays an important coordination role in BMP2-induced chondrogenic differentiation of stem cells and cartilage maintenance under oxidative stress, establishing the experimental basis for exploring the use of SIRT1 in cartilage defect repair.

RETRACTED ARTICLE: Exosome-delivered BMP-2 and polyaspartic acid promotes tendon bone healing in rotator cuff tear via Smad/RUNX2 signaling pathway

“…Mara et al also have showed that rhBMP-2 increases chondrocyte proliferation, mineralization, and differentiation, suggesting that BMP-2 was required for postnatal maintenance of osteochondral tissues of the temporomandibular joint [ 37 ]. SIRT1 promoted BMP-2-induced chondrogenic differentiation of MSCs and reduced the apoptosis and decomposition of the extracellular matrix under oxidative stress [ 38 ]. It has also been demonstrated that BMP-2 delivery by coacervate and gene therapy can promote human muscle-derived stem cell-mediated articular cartilage repair [ 23 ].…”

Histone Modifications and Chondrocyte Fate: Regulation and Therapeutic Implications

“…This suggests that SIRT1 may coordinate with HATs to modulate histone acetylation states in the promoter of COL2A1 gene, which subsequently regulate chondrocyte function. A recent study indicates that SIRT1 significantly upregulates the expression of SOX9, COL2A1, and ACAN in BMP2-induced chondrogenic differentiation of MSCs, and reduces apoptosis and decomposition of ECM under oxidative stress (Lu et al, 2020). These results indicate that SIRT1 exerts synergistic effect on BMP2-induced chondrogenesis of MSCs and plays an important role in blocking oxidative stress to create a more suitable microenvironment for chondrogenesis of MSCs.…”

A Comprehensive Analysis of SE-lncRNA/mRNA Differential Expression Profiles During Chondrogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells

“…Articular cartilage is a special tissue without blood vessels, nerves, and lymph, which leads to its poor self-repair ability ( Duarte Campos et al, 2012 ; Wang et al, 2019 ; Lu et al, 2020 ). Articular cartilage injury is a common clinical condition, but treatment is still difficult because of the characteristics of the articular cartilage ( Lu et al, 2020 ). BMSCs are the dominant seed cell source for tissue engineering ( Zhang et al, 2018 ; Ma et al, 2019 ).…”