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.
Highlights
There are many causes of cartilage injury, such as inflammation, aging, and oxidative stress [1, 2]
The results of real-time fluorescence quantitative PCR (Figure 1B, 1C) and western blotting showed that C3H10T1/2 cells transfected with the Ad-Bone morphogenetic protein 2 (BMP2) and Ad-Silent mating type information regulator homolog-1 (SIRT1) highly expressed BMP2 and SIRT1, but this did not occur in cells infected with Ad-green fluorescent protein (GFP) (Figure 1D, 1E)
We found that the expression of Sox9 in the Ad-SIRT1+Ad-BMP2 group was significantly higher than that in the Ad-BMP2 group, and the expression levels were significantly higher in both groups compared with that in the control group (Figure 2, P < 0.05)
Summary
There are many causes of cartilage injury, such as inflammation, aging, and oxidative stress [1, 2]. Mesenchymal stem cells (MSCs), one type of mesoderm stem cell with self-replication and multiple differentiation potential, can differentiate into bone, cartilage, or fat cells [7, 8]. Stem cell transplantation and/or gene-enhanced cartilage tissue may become potential methods for cartilage repair [9]. Bone morphogenetic proteins (BMPs) are growth and differentiation factors that belong to the transforming growth factor-β superfamily [10]. Bone morphogenetic protein 2 (BMP2), one of about 30 distinct BMPs [11], plays an important role in inducing osteogenesis and chondrogenesis of stem cells [12,13,14]. BMP2 has been proven to induce chondrogenic differentiation of human synovial MSCs in a dose-dependent manner and to be more capable of inducing chondrogenic differentiation than many other growth factors, such as transforming growth factor-β and insulin-like growth factor-1 (IGF-1) [15]
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