BMP6 participates in the pathogenesis of adolescent idiopathic scoliosis by regulating osteopenia

• Published in: Journal of cellular physiology Vol. 238; no. 11; pp. 2586 - 2599
• Main Authors: Tang, Hao, Li, Jiong, Li, Jia-Ke, He, Si-Han, Xiang, Gang, Rong, Rong, Liang, Zhuo-Tao, Zhang, Hong-Qi
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.11.2023
• Subjects: Adolescent; Adolescents; Animals; Bone Diseases, Metabolic - genetics; Bone Diseases, Metabolic - metabolism; Bone Marrow Cells - metabolism; Bone morphogenetic protein 6; Bone Morphogenetic Protein 6 - genetics; Bone turnover; Cbfa-1 protein; Cell Differentiation - genetics; Cells, Cultured; Differentiation (biology); Embryos; Humans; Mesenchymal stem cells; Metabolism; Osteogenesis - genetics; Osteopenia; Pathogenesis; Scoliosis; Scoliosis - genetics; Scoliosis - pathology; Spine; Spine - metabolism; Stem cells; Zebrafish; Zebrafish - genetics; adolescent idiopathic scoliosis (AIS); CAP1-217; adipogenic differentiation; bone marrow-derived mesenchymal stem cells (BMSCs); osteogenic differentiation; BMP6
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.31111

Adolescent idiopathic scoliosis (AIS) is a complex disease characterized by three-dimensional structural deformities of the spine. Its pathogenesis is associated with osteopenia. Bone-marrow-derived mesenchymal stem cells (BMSCs) play an important role in bone metabolism. We detected 1919 differentially expressed mRNAs and 744 differentially expressed lncRNAs in BMSCs from seven patients with AIS and five patients without AIS via high-throughput sequencing. Multiple analyses identified bone morphogenetic protein-6 (BMP6) as a hub gene that regulates the abnormal osteogenic differentiation of BMSCs in AIS. BMP6 expression was found to be decreased in AIS and its knockdown in human BMSCs significantly altered the degree of osteogenic differentiation. Additionally, CAP1-217 has been shown to be a potential upstream regulatory molecule of BMP6. We showed that CAP1-217 knockdown downregulated the expression of BMP6 and the osteogenic differentiation of BMSCs. Simultaneously, knockout of BMP6 in zebrafish embryos significantly increased the deformity rate. The findings of this study suggest that BMP6 is a key gene that regulates the abnormal osteogenic differentiation of BMSCs in AIS via the CAP1-217/BMP6/RUNX2 axis.