Sims Natalie A, Quinn Julian M W
Bone Cell Biology and Disease Unit, St Vincent's Institute of Medical Research , Melbourne, Victoria, Australia ; Department of Medicine at St Vincent's Hospital Melbourne, The University of Melbourne , Melbourne, Victoria, Australia.
Prince Henry's Institute, Monash Medical Centre , Melbourne, Victoria, Australia ; Department of Biochemistry and Molecular Biology, Monash University , Melbourne, Victoria, Australia.
Bonekey Rep. 2014 May 14;3:527. doi: 10.1038/bonekey.2014.22. eCollection 2014.
Bone remodeling in health and disease is carried out by osteoblasts and osteoclasts, which respectively produce bone matrix and resorb it. Endocrine and paracrine control of these cells can be direct, but they are also exerted indirectly, either by influencing progenitor cell differentiation or by stimulating paracrine signals from local accessory cells including osteocytes (which form a critical communication and regulation network within the bone matrix), macrophages and T lymphocytes. Here we review the osteotropic actions of the interleukin-6 family member cytokine oncostatin M (OSM), which is of particular interest because of its ability to stimulate bone accrual. OSM is produced within the bone microenvironment by cells of both mesenchymal and hematopoietic origin, including osteocytes, osteoblasts, macrophages and T lymphocytes, and can act via two receptor complexes: OSM receptor:gp130 and leukemia inhibitory factor receptor (LIFR):gp130. Although OSM can directly stimulate osteoblast mineralization activity and differentiation, it can also stimulate mesenchymal stem cell osteoblastic commitment at the expense of adipogenesis. In osteocytes, OSM can suppress the production of the bone formation inhibitor sclerostin, an action that is mediated by LIFR:gp130. OSM also stimulates the production of receptor activator of nuclear factor κB ligand by osteoblasts and thereby drives the formation of osteoclasts particularly in pathological conditions. Thus, cellular effects of OSM on bone metabolism include direct and indirect actions mediated by two related receptor/ligand complexes. OSM therefore provides an example of paracrine and endocrine control mechanisms that regulate bone mass by controlling both bone formation and resorption.
健康与疾病状态下的骨重塑由成骨细胞和破骨细胞完成，它们分别产生和吸收骨基质。对这些细胞的内分泌和旁分泌控制可以是直接的，但也可以通过影响祖细胞分化或刺激来自局部辅助细胞（包括骨细胞，其在骨基质内形成关键的通讯和调节网络）、巨噬细胞和T淋巴细胞的旁分泌信号间接发挥作用。在此，我们综述白细胞介素-6家族成员细胞因子制瘤素M（OSM）的促骨作用，因其刺激骨量增加的能力而备受关注。OSM由间充质和造血来源的细胞在骨微环境中产生，包括骨细胞、成骨细胞、巨噬细胞和T淋巴细胞，并可通过两种受体复合物发挥作用：OSM受体：gp130和白血病抑制因子受体（LIFR）：gp130。虽然OSM可以直接刺激成骨细胞矿化活性和分化，但它也可以刺激间充质干细胞向成骨细胞分化，同时抑制脂肪生成。在骨细胞中，OSM可以抑制骨形成抑制剂骨硬化蛋白的产生，这一作用由LIFR：gp130介导。OSM还刺激成骨细胞产生核因子κB受体激活剂配体，从而尤其在病理条件下驱动破骨细胞的形成。因此，OSM对骨代谢的细胞效应包括由两种相关受体/配体复合物介导的直接和间接作用。因此，OSM提供了一种通过控制骨形成和吸收来调节骨量的旁分泌和内分泌控制机制的实例。
