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

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 differenti...

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Bibliographic Details
Published in:Journal of cellular physiology 2023-11, Vol.238 (11), p.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: Article
Language:English
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
Osteogenesis - genetics
Osteopenia
Pathogenesis
Scoliosis
Scoliosis - genetics
Scoliosis - pathology
Spine
Spine - metabolism
Stem cells
Zebrafish
Zebrafish - genetics
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Summary: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.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.31111