title: Osteoimmunology: oncostatin M as a pleiotropic regulator of bone formation and resorption in health and disease.
abstract: 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.
authors.affiliation: 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.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Sims
authors.affiliation: Prince Henry's Institute, Monash Medical Centre , Melbourne, Victoria, Australia ; Department of Biochemistry and Molecular Biology, Monash University , Melbourne, Victoria, Australia.
authors.forename: Julian M W
authors.initials: JM
authors.lastname: Quinn