Int J Biol Macromol . 2024 Jan;254(Pt 2):127824. doi: 10.1016/j.ijbiomac.2023.127824. Epub 2023 Nov 2.

A novel lncRNA GM15416 regulates osteoblast apoptosis and differentiation through the c-Fos/Fas axis and mitigates osteoporosis

Affiliations

Affiliations

  • 1 Department of Orthopaedics, Lanzhou University Second Hospital, No. 82 Cuiying Gate, Chengguan District, Lanzhou 730030, Gansu, PR China; Gansu Province Clinical Medical Research Center for Orthopedics, No. 82 Cuiying Gate, Chengguan District, Lanzhou 730030, Gansu, PR China; Key Laboratory of Bone and joint Disease research of Gansu Province, No. 82 Cuiying Gate, Chengguan District, Lanzhou 730030, Gansu, PR China; Pain Department of the Second Hospital of Lanzhou University, No. 82 Cuiying Gate, Chengguan District, Lanzhou 730030, Gansu, Pr China.
  • 2 Department of Orthopaedics, Lanzhou University Second Hospital, No. 82 Cuiying Gate, Chengguan District, Lanzhou 730030, Gansu, PR China; Gansu Province Clinical Medical Research Center for Orthopedics, No. 82 Cuiying Gate, Chengguan District, Lanzhou 730030, Gansu, PR China; Key Laboratory of Bone and joint Disease research of Gansu Province, No. 82 Cuiying Gate, Chengguan District, Lanzhou 730030, Gansu, PR China.
  • 3 Department of Orthopaedics, Lanzhou University Second Hospital, No. 82 Cuiying Gate, Chengguan District, Lanzhou 730030, Gansu, PR China; Gansu Province Clinical Medical Research Center for Orthopedics, No. 82 Cuiying Gate, Chengguan District, Lanzhou 730030, Gansu, PR China; Key Laboratory of Bone and joint Disease research of Gansu Province, No. 82 Cuiying Gate, Chengguan District, Lanzhou 730030, Gansu, PR China. Electronic address: ery_gengb@lzu.edu.cn.
  • 4 Department of Orthopaedics, Lanzhou University Second Hospital, No. 82 Cuiying Gate, Chengguan District, Lanzhou 730030, Gansu, PR China; Gansu Province Clinical Medical Research Center for Orthopedics, No. 82 Cuiying Gate, Chengguan District, Lanzhou 730030, Gansu, PR China; Key Laboratory of Bone and joint Disease research of Gansu Province, No. 82 Cuiying Gate, Chengguan District, Lanzhou 730030, Gansu, PR China. Electronic address: xiayy@lzu.edu.cn.

Abstract

Osteoporosis (OP) is a common systemic bone disorder, and the programmed cell death of osteoblasts is closely linked to the development of osteoporosis. Previous studies have shown that c-fos can cause osteoblast apoptosis. Furthermore, it has been demonstrated that long non-coding RNA (lncRNA) plays a pervasive role in regulating the biology of osteoblasts. Nevertheless, the precise role and mechanism of long non-coding RNA (lncRNA) in relation to c-Fos at the transcriptional level in osteoblast cell death remain uncertain. Compared with normal osteoblasts, serum deprivation resulted in significant upregulation of the transcription factor c-Fos and apoptosis-related Fas proteins in osteoblasts. In addition, the expression of lncRNA GM15416 related to c-Fos was significantly increased. The results showed that overexpression of c-Fos leads to an increase in downstream Fas protein, which subsequently leads to osteoblast apoptosis and hinders osteogenesis. On the contrary, a decrease in lncRNA GM15416 expression leads to a decrease in c-Fos/Fas expression, which hinders osteoblast apoptosis and promotes osteogenesis. Our results suggest that lncRNA GM15416 exerts inhibitory effects on osteoblast apoptosis and acts as a preventive factor against osteoporosis. As a result, GM15416 emerges as an important lncRNA associated with osteoporosis and holds potential as a future therapeutic target.

Keywords: C-Fos; Osteoporosis; lncRNA GM15416.

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