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MicroRNA-874 targeting SUFU involves in osteoblast proliferation and differentiation in osteoporosis rats through the Hedgehog signaling pathway

Lin, Jian-Chun, Liu, Zhong-Guo, Yu, Bin, Zhang, Xian-Rong
Biochemical and biophysical research communications 2018 v.506 no.1 pp. 194-203
apoptosis, bone formation, bone morphogenetic proteins, calcium, cell viability, females, laboratory animals, metabolism, mice, microRNA, osteoblasts, osteoporosis, proliferating cell nuclear antigen, public health, rats, signal transduction, skeletal development, tissues
Osteoporosis is widely viewed as a major public health concern, but the exact magnitude of the problem is uncertain. MicroRNAs play a key role in maintaining bone development and metabolism. This study aims to investigate the effects that microRNA-874 (miR-874) has on osteoblast proliferation and differentiation in osteoporosis rats by targeting SUFU through the Hedgehog signaling pathway. Twenty Wistar female rats were selected for following experiment, and another 20 rats were served as the normal group. Their osteogenic tissues were obtained and the positive expression of SUFU in tissues was determined. Rat osteoblasts were isolated and. The targeting relationship between SUFU and miR-874 was verified and the expression of miR-874, SUFU, Sonic Hedgehog (Shh), Ptch, Smoothened (Smo), bone morphogenetic protein (BMP2), Runx2, proliferating cell nuclear antigen (PCNA) and Bcl-2 associated X protein (Bax) were identified. Besides, cell viability apoptosis, and differentiation were confirmed respectively. Moreover, calcium nodules were observed. Overexpression of SUFU and Bax but lower expression of miR-874, Shh, Ptch, Smo, BMP2, Runx2, and PCNA were found in osteoporosis mice. Besides, elevated expression of miR-874, Shh, Ptch, Smo, BMP2, Runx2 and PCNA, as well as increased cell viability, ALP activity and calcium nodules but decreased expression of SUFU and Bax, and reduced cell apoptosis were confirmed when treated with miR-874 mimic. And it is reciprocal when miR-874 was inhibited. Our study demonstrated that through targeted inhibition of SUFU and activation of Hedgehog signaling pathway, miR-874 could promote the proliferation and differentiation of osteoblasts in osteoporosis rats.