Department of Cell Biology and Neuroscience and Stem Cell Center, College of Natural and Agricultural Sciences, University of California Riverside, 1113 Biological Sciences Building, Riverside, CA, 92521, USA.
Curr Osteoporos Rep. 2017 Aug;15(4):353-366. doi: 10.1007/s11914-017-0379-7.
Osteogenesis is a complex process involving the specification of multiple progenitor cells and their maturation and differentiation into matrix-secreting osteoblasts. Osteogenesis occurs not only during embryogenesis but also during growth, after an injury, and in normal homeostatic maintenance. While much is known about osteogenesis-associated regulatory genes, the role of microRNAs (miRNAs), which are epigenetic regulators of protein expression, is just beginning to be explored. While miRNAs do not abrogate all protein expression, their purpose is to finely tune it, allowing for a timely and temporary protein down-regulation.
The last decade has unveiled a multitude of miRNAs that regulate key proteins within the osteogenic lineage, thus qualifying them as "ostemiRs." These miRNAs may endogenously target an activator or inhibitor of differentiation, and depending on the target, may either lead to the prolongation of a progenitor maintenance state or to early differentiation. Interestingly, cellular identity seems intimately coupled to the expression of miRNAs, which participate in the suppression of previous and subsequent differentiation steps. In such cases where key osteogenic proteins were identified as direct targets of miRNAs in non-bone cell types, or through bioinformatic prediction, future research illuminating the activity of these miRNAs during osteogenesis will be extremely valuable. Many bone-related diseases involve the dysregulation of transcription factors or other proteins found within osteoblasts and their progenitors, and the dysregulation of miRNAs, which target such factors, may play a pivotal role in disease etiology, or even as a possible therapy.
成骨作用是一个复杂的过程，涉及多个祖细胞的特化及其成熟和分化为分泌基质的成骨细胞。成骨作用不仅发生在胚胎发生过程中，而且发生在生长、损伤后和正常的体内平衡维持过程中。虽然人们对与成骨作用相关的调节基因了解很多，但微 RNA（miRNA）的作用——即蛋白质表达的表观遗传调节剂——才刚刚开始被探索。虽然 miRNA 不会消除所有蛋白质的表达，但它们的目的是精细地调节它，从而实现及时和暂时的蛋白质下调。
过去十年揭示了许多调节成骨谱系中关键蛋白的 miRNA，从而将它们鉴定为“ostemiR”。这些 miRNA 可能内源性地靶向分化的激活剂或抑制剂，并且根据靶标，可能导致祖细胞维持状态的延长或早期分化。有趣的是，细胞身份似乎与 miRNA 的表达密切相关，miRNA 参与抑制先前和随后的分化步骤。在这种情况下，关键成骨蛋白被鉴定为非骨细胞类型中 miRNA 的直接靶标，或者通过生物信息学预测，阐明这些 miRNA 在成骨过程中的活性的未来研究将非常有价值。许多与骨骼相关的疾病涉及转录因子或成骨细胞及其前体细胞中发现的其他蛋白质的失调，以及靶向这些因子的 miRNA 的失调，可能在疾病发病机制中发挥关键作用，甚至可能作为一种潜在的治疗方法。
