Abstract
Neural cell adhesion molecule (NCAM) is involved in cell multi-directional differentiation, but its role in osteoblast differentiation is still poorly understood. In the present study, we investigated whether and how NCAM regulates osteoblastic differentiation. We found that NCAM silencing inhibited osteoblast differentiation in pre-osteoblastic MC3T3-E1 cells. The function of NCAM was further confirmed in NCAM-deficient mesenchymal stem cells (MSCs), which also had a phenotype with reduced osteoblastic potential. Moreover, NCAM silencing induced decrease of Wnt/β-catenin and Akt activation. The Wnt inhibitor blocked osteoblast differentiation, and the Wnt activator recovered osteoblast differentiation in NCAM-silenced MC3T3-E1 cells. We lastly demonstrated that osteoblast differentiation of MC3T3-E1 cells was inhibited by the PI3K-Akt inhibitor. In conclusion, these results demonstrate that NCAM silencing inhibited osteoblastic differentiation through inactivation of Wnt/β-catenin and PI3K-Akt signaling pathways.
Highlights
IntroductionOsteoporosis (OP) is one of the most common bone disorders in human beings, its incidence increases with age, especially in postmenopausal women because of the decrease in estrogen [1, 2]
We demonstrated that Neural cell adhesion molecule (NCAM) enhances insulin sensitivity and promotes adipocyte differentiation, and we further found that NCAM inhibits hypertrophic chondrocyte differentiation and reduces chondrocyte hypertrophy in experimental osteoarthritis model [14, 15]
Calcium deposition was visualized by Alizarin Red staining and quantitative analysis, the calcium content was significantly decreased in Sh-NCAM cells as compared to Sh-ctl MC3T3-E1 cells (Figures 1H, I)
Summary
Osteoporosis (OP) is one of the most common bone disorders in human beings, its incidence increases with age, especially in postmenopausal women because of the decrease in estrogen [1, 2]. OP is characterized by a reduction in bone mineral density, which is mainly due to the imbalance of bone tissue formation and absorption [5, 6]. Bone homeostasis depends on the balance between osteoblasts and osteoclasts, OP occurs as a result of the decrease of osteoblast-induced bone formation and the increase of osteoclast-induced bone absorption. Bone weakness and fracture are common in patients with OP because of their low bone mass and quality. Abnormal proliferation and differentiation of osteoblasts were shown involved in reduction of bone mass [7, 8]. Study on the molecular mechanisms of osteoblastic differentiation is helpful to understand the pathogenesis of OP and develop new strategies for OP treatment
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