STRA6 as a possible candidate gene for pathogenesis of osteoporosis from RNA‑seq analysis of human mesenchymal stem cells

Song,Insun; Choi,Yong  Jun; Jin,Yilan; Kim,Jung‑Woo; Koh,Jeong‑Tae; Ji,Hyung  Min; Jeong,Seon‑Yong; Won,Ye‑Yeon; Kim,Won; Chung,Yoon‑Sok

doi:10.3892/mmr.2017.7072

STRA6 as a possible candidate gene for pathogenesis of osteoporosis from RNA‑seq analysis of human mesenchymal stem cells

Authors:
- Insun Song
- Yong Jun Choi
- Yilan Jin
- Jung‑Woo Kim
- Jeong‑Tae Koh
- Hyung Min Ji
- Seon‑Yong Jeong
- Ye‑Yeon Won
- Won Kim
- Yoon‑Sok Chung
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Affiliations: School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea, Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon 16499, Republic of Korea, Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of Korea, Department of Orthopedic Surgery, Ajou University School of Medicine, Suwon 16499, Republic of Korea, Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Republic of Korea
Published online on: July 21, 2017 https://doi.org/10.3892/mmr.2017.7072
Pages: 4075-4081
Copyright: © Song et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

To identify novel candidate genes associated with osteoporosis, RNA‑sequence analysis of human mesenchymal stem cells (hMSCs) from patients with osteoporosis (G3) and osteopenia (G2), and healthy controls (G1) was performed. Differentially expressed genes (DEGs) from among the three groups were identified. DEGs were separated into nine groups according to their gene expression patterns: UU (up and up), UF (up and flat), UD (up and down), FU (flat and up), FF (flat and flat), FD (flat and down), DU (down and up), DF (down and flat), and DD (down and down). Among the 42 DEGs between G3 and G1, eight candidate genes, namely stimulated by retinoic acid 6 (STRA6), melanophilin, neurotrophic receptor tyrosine kinase 2, cartilage oligomeric matrix protein, collagen type XI α 1 chain, integrin subunit β 2, monooxygenase DBH‑like 1 and selenoprotein P, were selected, as they demonstrated consistent gene expression patterns of UU, FU, FD, and DD. Among these eight genes, STRA6 was highly expressed in the osteoporosis group and based on additional data from quantitative polymerase chain reaction analysis, it was selected for further study. In order to investigate whether STRA6 served a functional role in osteoblast or adipocyte differentiation, the effects of STRA6 expression changes in pluripotent stem cell C3H10T1/2, preosteoblast MC3T3‑E1 and stromal ST2 cell lines were examined. Bone morphogenetic protein 2 enhanced STRA6 expression only at the early stage of osteoblast differentiation, and overexpression of STRA6 temporally inhibited the expression of osteoblastogenesis markers, including runt related transcription factor 2, bone sialoprotein and osteocalcin. Furthermore, the knockdown of STRA6 slightly enhanced nodule formation at the late stage of osteoblast differentiation, and overexpression of STRA6 in ST2 cells enhanced adipocyte differentiation. Taken together, STRA6 expression could be associated with the pathogenesis of osteoporosis by promoting adipocyte differentiation over osteoblast differentiation in the hMSC population.