Department of Spinal Surgery, The Third Hospital of Hebei Medical University, No. 139, Ziqiang Road, Shijiazhuang 050051, Hebei, P.R. China.
Department of Orthopedics, Tangshan Gongren Hospital, No. 27, Wenhua Road, Tangshan 063000, Hebei, P.R. China.
Exp Anim. 2023 Aug 7;72(3):413-424. doi: 10.1538/expanim.22-0129. Epub 2023 Apr 5.
The imbalance of bone resorption and bone formation causes osteoporosis (OP), a common skeletal disorder. Decreased osteogenic activity was found in the bone marrow cultures from N-acetylglucosaminyl transferase V (MGAT5)-deficient mice. We hypothesized that MGAT5 was associated with osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and involved in the pathological mechanisms of osteoporosis. To test this hypothesis, the mRNA and protein expression levels of MGAT5 were determined in bone tissues of ovariectomized (OVX) mice, a well-established OP model, and the role of MGAT5 in osteogenic activity was investigated in murine BMSCs. As expected, being accompanied by the loss of bone mass density and osteogenic markers (runt-related transcription factor 2, osteocalcin and osterix), a reduced expression of MGAT5 in vertebrae and femur tissues were found in OP mice. In vitro, knockdown of Mgat5 inhibited the osteogenic differentiation potential of BMSCs, as evidenced by the decreased expressions of osteogenic markers and less alkaline phosphatase and alizarin red S staining. Mechanically, knockdown of Mgat5 suppressed the nuclear translocation of β-catenin, thereby downregulating the expressions of downstream genes c-myc and axis inhibition protein 2, which were also associated with osteogenic differentiation. In addition, Mgat5 knockdown inhibited bone morphogenetic protein (BMP)/transforming growth factor (TGF)-β signaling pathway. In conclusion, MGAT5 may modulate the osteogenic differentiation of BMSCs via the β-catenin, BMP type 2 (BMP2) and TGF-β signals and involved in the process of OP.
破骨细胞和成骨细胞活性失衡会导致骨质疏松症（OP），这是一种常见的骨骼疾病。在 N-乙酰氨基葡萄糖基转移酶 V（MGAT5）缺陷小鼠的骨髓培养物中发现成骨活性降低。我们假设 MGAT5 与骨髓间充质干细胞（BMSCs）的成骨分化有关，并参与骨质疏松症的病理机制。为了验证这一假设，我们在去卵巢（OVX）小鼠的骨组织中测定了 MGAT5 的 mRNA 和蛋白表达水平，该模型是一种成熟的 OP 模型，并研究了 MGAT5 在小鼠 BMSCs 成骨活性中的作用。正如预期的那样，伴随着骨量密度和成骨标志物（Runt 相关转录因子 2、骨钙素和骨桥蛋白）的丧失，在 OP 小鼠的椎骨和股骨组织中发现 MGAT5 的表达减少。在体外，Mgat5 的敲低抑制了 BMSCs 的成骨分化潜能，这表现在成骨标志物的表达减少以及碱性磷酸酶和茜素红 S 染色减少。在机制上，Mgat5 的敲低抑制了β-连环蛋白的核易位，从而下调下游基因 c-myc 和轴抑制蛋白 2 的表达，这些基因也与成骨分化有关。此外，Mgat5 的敲低抑制了骨形态发生蛋白（BMP）/转化生长因子（TGF）-β信号通路。总之，MGAT5 可能通过β-连环蛋白、BMP 型 2（BMP2）和 TGF-β信号调节 BMSCs 的成骨分化，并参与 OP 过程。
