2023, Vol. 27 ›› Issue (10): 1578-1583

TLN1 negatively regulates adipogenic differentiation of bone marrow mesenchymal stem cells through activating the beta-catenin signaling pathway

Huang Hongyan1, Ke Haoteng2, Ye Weijia2, Deng Huazong2, Wang Tao2, Cai Mingxi2, Chen Qifan2, Cen Shuizhong2   

Abstract: BACKGROUND: The balance between osteogenic and adipogenic differentiation in bone marrow mesenchymal stem cells plays a key role in bone metabolic diseases. Our previous study confirmed that TLN1 can regulate osteogenic differentiation of bone marrow mesenchymal stem cells, but its effect on adipogenic differentiation of bone marrow mesenchymal stem cells remains unclear.
OBJECTIVE: To investigate the role and mechanism of TLN1 in the adipogenic differentiation of bone marrow mesenchymal stem cells.
METHODS: Bone marrow mesenchymal stem cells were induced to adipogenic differentiation and TLN1 expression was detected by qRT-PCR and western blot assay. CCK-8 was used to detect the proliferation of bone marrow mesenchymal stem cells after TLN1 knockdown. The Oil red O staining and quantification were performed after adipogenic induction. Besides, qRT-PCR was used to detect the gene expression levels of the key molecules of adipogenic differentiation of bone marrow mesenchymal stem cells including PPAR-γ and C/EBP-α. Western blot assay was used to detect the classic pathway of adipogenesis. Meanwhile, TLN1 was knockdown and β-catenin activator was added to detect the adipogenic differentiation of bone marrow mesenchymal stem cells, to explore the specific molecular mechanism of TLN1 regulating adipogenesis.
RESULTS AND CONCLUSION: TLN1 expression was down-regulated during adipogenic differentiation of bone marrow mesenchymal stem cells. TLN1 knockdown had no significant effect on the proliferation of bone marrow mesenchymal stem cells, but significantly increased the adipogenic induction of bone marrow mesenchymal stem cells. TLN1 knockdown could inhibit the expression of active β-catenin, while activation of β-catenin signaling pathway could reverse the enhancement of adipogenesis mediated by TLN1 knockdown. These findings suggest that TLN1 expression is gradually down-regulated during the adipogenic differentiation of bone marrow mesenchymal stem cells, and TLN1 knockdown can promote the adipogenic differentiation of bone marrow mesenchymal stem cells by inhibiting β-catenin signaling pathway.
Key words: mesenchymal stem cell, TLN1, adipogenic differentiation, β-catenin, signaling pathway, tissue engineering