lncRNA SERPINB9P1 Regulates SIRT6 Mediated Osteogenic Differentiation of BMSCs via miR-545-3p

• Published in: Calcified tissue international Vol. 112; no. 1; pp. 92 - 102
• Main Authors: Wu, Min, Dai, Min, Liu, Xuqiang, Zeng, Qunqun, Lu, Yingjie
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.01.2023; Springer Nature B.V
• Subjects: Biochemistry; Biomedical and Life Sciences; Bone marrow; Cell Biology; Cell Differentiation - genetics; Cells, Cultured; Endocrinology; Humans; Immunoprecipitation; Life Sciences; Mesenchymal Stem Cells; MicroRNAs - genetics; MicroRNAs - metabolism; Mineralization; Non-coding RNA; Original Research; Orthopedics; Osteogenesis - genetics; Osteoporosis; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA-binding protein; Sirtuins - metabolism; Stromal cells; lncRNA SERPINB9P1; Osteoporosis; SIRT6; miR-545-3p
• ISSN: 1432-0827; 0171-967X; 1432-0827
• DOI: 10.1007/s00223-022-01034-3

Evidence has shown that the altered osteogenic differentiation of human bone marrow stromal cells (BMSCs) under pathological conditions, such as osteoporosis, lead to the imbalance of bone tissue generation and destruction. Recent studies have indicated that long noncoding RNAs may play a role in regulating BMSCs osteogenic differentiation. This contributed to our impetus to move forward with the investigation of the function of lncRNA SERPINB9P1 in osteogenic differentiation of BMSCs and the potential mechanisms involved. Osteogenic differentiation of BMSCs was induced by osteogenic medium. Relative expression of lncRNA SERPINB9P1 and miR-545-3p were tested by qRT-PCR. Osteogenic mineralization was examined by Alizarin S Red staining, ALP staining, and ALP activity assay. Expression of osteoblastic markers were detected by Western blot. RNA-binding protein immunoprecipitation and dual-luciferase reporter assays were performed to test the interaction between lncRNA SERPINB9P1 and miR-545-3p. BMSCs osteogenic differentiation resulted in LncRNA SERPINB9P1 overexpression while miR-545-3p inhibition. Functional assays suggest that knockdown of lncRNA SERPINB9P1 or overexpression of miR-545-3p both inhibit BMSC osteogenic differentiation. lncRNA SERPINB9P1 was proven to regulate the osteogenic differentiation of BMSCs by altering SIRT6 expression through its suppressive effects on miR-545-3p. lncRNA SERPINB9P1 promotes osteogenic differentiation of BMSCs through the miR-545-3p/SIRT6 pathway.