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Osteoclast Derivation from Mouse Bone Marrow
Published on: November 6, 2014
MicroRNA-31a-5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment
Rongyao Xu1,2, Xiang Shen1,2, Yameng Si1,2
1Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
Abstract:
The alteration of age-related molecules in the bone marrow microenvironment is one of the driving forces in osteoporosis. These molecules inhibit bone formation and promote bone resorption by regulating osteoblastic and osteoclastic activity, contributing to age-related bone loss. Here, we observed that the level of microRNA-31a-5p (miR-31a-5p) was significantly increased in bone marrow stromal cells (BMSCs) from aged rats, and these BMSCs demonstrated increased adipogenesis and aging phenotypes as well as decreased osteogenesis and stemness. We used the gain-of-function and knockdown approach to delineate the roles of miR-31a-5p in osteogenic differentiation by assessing the decrease of special AT-rich sequence-binding protein 2 (SATB2) levels and the aging of BMSCs by regulating the decline of E2F2 and recruiting senescence-associated heterochromatin foci (SAHF). Notably, expression of miR-31a-5p, which promotes osteoclastogenesis and bone resorption, was markedly higher in BMSCs-derived exosomes from aged rats compared to those from young rats, and suppression of exosomal miR-31a-5p inhibited the differentiation and function of osteoclasts, as shown by elevated RhoA activity. Moreover, using antagomiR-31a-5p, we observed that, in the bone marrow microenvironment, inhibition of miR-31a-5p prevented bone loss and decreased the osteoclastic activity of aged rats. Collectively, our results reveal that miR-31a-5p acts as a key modulator in the age-related bone marrow microenvironment by influencing osteoblastic and osteoclastic differentiation and that it may be a potential therapeutic target for age-related osteoporosis.
Insights
MicroRNA-31a-5p (miR-31a-5p) increases with age in bone marrow, promoting osteoporosis by impairing bone formation and enhancing bone breakdown. Inhibiting miR-31a-5p in aged rats reversed bone loss, suggesting it as a therapeutic target.
Area of Science:
- * Molecular biology
- * Gerontology
- * Bone biology
Background:
- * Age-related osteoporosis is driven by molecular changes in the bone marrow microenvironment.
- * These changes affect bone-forming osteoblasts and bone-resorbing osteoclasts, leading to bone loss.
- * MicroRNAs (miRNAs) are implicated in regulating cellular functions relevant to bone metabolism.
Purpose of the Study:
- * To investigate the role of microRNA-31a-5p (miR-31a-5p) in the aging bone marrow microenvironment and its contribution to osteoporosis.
- * To determine the impact of miR-31a-5p on bone marrow stromal cells (BMSCs) and their differentiation potential.
- * To explore the therapeutic potential of targeting miR-31a-5p for age-related bone loss.
Main Methods:
- * Analysis of miR-31a-5p levels in BMSCs from young and aged rats.
- * Gain-of-function and knockdown experiments to assess miR-31a-5p's effect on BMSC osteogenesis and aging.
- * Examination of miR-31a-5p expression in exosomes derived from BMSCs.
- * In vivo studies using antagomiR-31a-5p to evaluate its effect on bone loss and osteoclast activity in aged rats.
Main Results:
- * miR-31a-5p levels were significantly elevated in aged rat BMSCs, correlating with increased adipogenesis, aging phenotypes, and reduced osteogenesis and stemness.
- * miR-31a-5p negatively regulated osteogenic differentiation by decreasing special AT-rich sequence-binding protein 2 (SATB2) and promoted BMSC aging via E2F2 and senescence-associated heterochromatin foci (SAHF).
- * Exosomal miR-31a-5p from aged BMSCs promoted osteoclastogenesis and bone resorption, with suppression inhibiting osteoclast differentiation and function (e.g., RhoA activity).
- * In vivo inhibition of miR-31a-5p using antagomiR-31a-5p prevented bone loss and reduced osteoclastic activity in aged rats.
Conclusions:
- * miR-31a-5p is a key regulator in the aging bone marrow microenvironment, influencing both osteoblastic and osteoclastic differentiation.
- * Elevated miR-31a-5p contributes to age-related bone loss by promoting BMSC aging and enhancing osteoclast activity.
- * Targeting miR-31a-5p presents a promising therapeutic strategy for age-related osteoporosis.
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