Research Highlights
- Subject Categories:
Published online: 23 December 2009 | doi:10.1038/nchina.2009.243
Medical genetics: The mutation responsible for osteoporosis
Felix Cheung
Abstract
Researchers in Changsha have identified a novel microRNA, the mutation of which may be responsible for osteoporosis
Original article citation
et al. A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans. J. Clin. Invest. 119, 3666–3677 (2009).Introduction
© (2009) istockphoto.com/Aimin Tang
Osteoporosis, the rapid reduction of bone mass, is a crippling condition that affects one in every three women and one in every five men over the age of 50. Recent studies have suggested that microRNAs — single-stranded RNAs that regulate gene expression — may play a role in osteoporosis, but it remains unclear what this role, if any, may be. Xianghang Luo and co-workers at Central South University in Changsha1 have now identified miR-2861 as a novel microRNA that regulates osteoblast differentiation and bone formation. More importantly, they showed that miR-2861 mutation was the cause of primary osteoporosis in two siblings.
Bone morphogenetic proteins (BMPs) are growth factors known for their ability to induce osteoblast differentiation. The researchers studied the effects of miR-2861 in mouse bone marrow stromal cells. They found that silencing miR-2861 attenuated BMP2-induced osteoblast differentiation, whereas overexpressing miR-2861 promoted BMP2-induced osteoblast differentiation.
Apparently, the microRNA can achieve this by regulating the gene expression of histone deacetylase 5 (HDAC5), an enhancer of Runx2 degradation (Runx2 is a transcription factor for osteoblast differentiation). Silencing miR-2861 also inhibited bone formation and reduced bone mass in mice.
The researchers also examined miR-2861 expression in two siblings with primary osteoporosis. The bones of both siblings lacked miR-2861 expression, and displayed elevated HDAC5 protein levels and reduced Runx2 expression. Further studies confirmed that miR-2861 mutation was the cause of the siblings' bone conditions.
The authors of this work are from:
Institute of Endocrinology and Metabolism, Second Xiangya Hospital, Central South University, Changsha, China.
Reference
- Li, H. et al. A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans. J. Clin. Invest. 119, 3666–3677 (2009). | Article | PubMed | OpenURL | | ChemPort |
