Green Alanna C, Martin T John, Purton Louise E
St Vincent's Institute, Fitzroy, Victoria 3065, Australia; Department of Medicine at St. Vincent's Hospital, The University of Melbourne, Victoria 3065, Australia.
St Vincent's Institute, Fitzroy, Victoria 3065, Australia; Department of Medicine at St. Vincent's Hospital, The University of Melbourne, Victoria 3065, Australia.
J Steroid Biochem Mol Biol. 2016 Jan;155(Pt A):135-46. doi: 10.1016/j.jsbmb.2015.09.036. Epub 2015 Nov 4.
Vitamin A and retinoid derivatives are recognized as morphogens that govern body patterning and skeletogenesis, producing profound defects when in excess. In post-natal bone, both high and low levels of vitamin A are associated with poor bone heath and elevated risk of fractures. Despite this, the precise mechanism of how retinoids induce post-natal bone changes remains elusive. Numerous studies have been performed to discover how retinoids induce these changes, revealing a complex morphogenic regulation of bone through interplay of different cell types. This review will discuss the direct and indirect effects of retinoids on mediators of bone turnover focusing on differentiation and activity of osteoblasts and osteoclasts and explains why some discrepancies in this field have arisen. Importantly, the overall effect of retinoids on the skeleton is highly site-specific, likely due to differential regulation of osteoblasts and osteoclasts at trabecular vs. cortical periosteal and endosteal bone surfaces. Further investigation is required to discover the direct gene targets of retinoic acid receptors (RARs) and molecular mechanisms through which these changes occur. A clear role for RARs in regulating bone is now accepted and the therapeutic potential of retinoids in treating bone diseases has been established.
维生素A和类视黄醇衍生物被认为是调控身体模式形成和骨骼生成的形态发生素，过量时会产生严重缺陷。在出生后的骨骼中，维生素A水平过高或过低均与骨骼健康状况不佳及骨折风险增加有关。尽管如此，类视黄醇如何诱导出生后骨骼变化的确切机制仍不清楚。人们已经进行了大量研究来探索类视黄醇如何引发这些变化，结果揭示了通过不同细胞类型之间的相互作用对骨骼进行的复杂形态发生调控。本综述将讨论类视黄醇对骨转换介质的直接和间接影响，重点关注成骨细胞和破骨细胞的分化与活性，并解释该领域中为何会出现一些差异。重要的是，类视黄醇对骨骼的总体影响具有高度的部位特异性，这可能是由于在小梁骨与皮质骨的骨膜和骨内膜表面，成骨细胞和破骨细胞受到不同的调控。需要进一步研究以发现视黄酸受体（RARs）的直接基因靶点以及这些变化发生的分子机制。目前，RARs在调节骨骼方面的明确作用已得到认可，并且类视黄醇在治疗骨疾病方面的治疗潜力也已得到证实。
