The role of adipocyte fatty acid binding protein (A-FABP) in the regulation of bone metabolism

Abstract

<p><strong>Introduction</strong>: Adipocyte fatty acid-binding protein (A-FABP) is a fat-derived hormone. Circulating A-FABP is elevated in obese subjects and is closely associated with cardio-metabolic diseases including type 2 diabetes, atherosclerosis and ischemic stroke. Treatment of a REV-ERB agonist (SR9009) was shown to inhibit osteoclast differentiation and alleviate ovariectomy-induced bone loss in mice associating with an increased expression of A-FABP. Pharmacological inhibition of A-FABP using its selective inhibitor BMS309403, reversed SR9009-mediated suppression on osteoclast differentiation. Here, we investigate the role of A-FABP in the regulation of bone remodeling.</p><p><strong>Results</strong>: A-FABP deficient mice exhibit a significant reduction in bone density comparing to their wildtype littermates. In vitro studies demonstrated that the expression of A-FABP is increased along osteoblast differentiation while decreased along osteoclast differentiation. Treatment of BMS309403 promotes differentiation of pro-osteoclasts to osteoclasts while inhibits differentiation of pro-osteoblasts to osteoblasts. On the contrary, treatment of recombinant A-FABP inhibits differentiation of pro-osteoclasts to osteoclasts while promotes differentiation of pro-osteoblasts to osteoblasts. Mechanistically, our data suggest that A-FABP induces osteoblast differentiation by promoting β-catenin nuclear translocation and activating p38/ERK signlaing while A-FABP inhibits osteoclast differentiation by inactivating p38/ERK/JNK signaling pathway.</p><p><strong>Conclusion</strong>: A-FABP is a crucial factor in maintaining bone homeostasis.</p><p><strong>Acknowledgement:</strong> This study is supported by Health Medical Research Fund (09201826).</p>