BBOX1-AS1 ameliorate bone fracture by regulating cell viability and apoptosis of osteoblasts.

BACKGROUND

The main objective of this study was to explore the role of BBOX1-AS1 in the osteogenic differentiation of osteoporosis (OP) and MC3T3-E1 cells.

METHODS

Bone tissue/serum samples from OP-Frx (n = 75), OP-non-Frx (n = 62), and healthy controls (n = 90) were collected. MC3T3-E1 cells were induced for osteogenic differentiation. RT-qPCR detected expression of BBOX1-AS1, miR-134-5p, Follistatin-like 1 (FSTL1), and osteogenic markers (Anxa8, Runx2, Col1a1). Cell viability (CCK-8), alkaline phosphatase (ALP) activity, and apoptosis (flow cytometry) were measured. Dual-luciferase reporter and RNA binding protein immunoprecipitation (RIP) assays verified molecular interactions.

RESULTS

Compared with controls, BBOX1-AS1 and FSTL1 were significantly upregulated in OP patients, whereas OP-Frx was dramatically upregulated compared with OP-non-Frx, while miR-134-5p was markedly downregulated. Meanwhile, during MC3T3-E1 osteogenic differentiation, BBOX1-AS1 and FSTL1 expression decreased, while miR-134-5p expression increased. Furthermore, silencing of BBOX1-AS1 and FSTL1 promoted cell viability, ALP activity, and Anxa8, Runx2, and Col1a1 levels and reduced apoptosis. Conversely, inhibition of miR-134-5p had an inverse effect. The above data demonstrate that BBOX1-AS1 modulates osteoblast activity and apoptosis by regulating the miR-134-5p/FSTL1 axis.

CONCLUSION

Downregulation of BBOX1-AS1 by targeting the miR-134-5p/FSTL1 axis promotes MC3T3-E1 osteogenic differentiation. Our study opens up new avenues for the diagnosis and treatment of osteoporotic fractures.