Osteoimmunology: an interdisciplinary approach to studying the relationships between immune and bone cells

Abstract

In this review, we discuss molecular and cellular mechanisms underlying cross-talk between immune cells and bone cells, both in healthy conditions and in some diseases. We provide short description of the main cell populations of bone tissue, i.e., osteoblasts, osteoclasts, osteocytes, bone marrow macrophages, OsteoMacs, and their effects on immune cells during bone modeling and remodeling. The data are presented on regulatory molecular pathways of bone marrow cell activity, T and B cells, macrophages, and formation of “endosteal niche” by the bone cells. We describe the key system of bone tissue homeostasis: RANK/RANKL/ OPG, which regulates differentiation of osteoclasts and bone destruction. In addition, RANK/RANKL/ OPG system modulates maturation and activity of various T and B cell subsets. We present the data on pleiotropic effects of T cells, B cells, dendritic cells, macrophage subpopulations, Tregs, NK cells, neutrophils upon differentiation and function of osteoblasts and osteoclasts. These effects promote accumulation and maintenance of the bone mass. We describe mechanisms of these effects based on direct cell-to-cell contacts and various soluble mediators and intracellular signaling pathways. A brief characteristic of some diseases is provided with concomitant dysfunction of immune cells and bone cells which play a decisive pathogenetic role (fractures, rheumatoid arthritis, periodontitis, postmenopausal osteoporosis, multiple myeloma). It was shown that the destructive bone inflammation, both in RA and periodontitis, leads to loss of bone mass, being featured by similar pathophysiological mechanisms involving immune and bone cell populations. Therapy of these diseases requires newer treatment strategies aimed not only at pro-inflammatory cytokines, but for increased bone resorption. We describe involvement of activated T cells, their cytokines into the pathogenesis of postmenopausal osteoporosis, thus providing a rationale for the novel term of “immunoporosis”, coined in 2018. The relationships between multiple myeloma cells and bone marrow microenvironment are provided. This cross-talk is based on contact cell-cell interactions, as well as due to effects of soluble mediators upon osteoclasts, stromal cells, and osteoblasts. These effects result in osteolysis, loss of bone mass, and myeloma progression. In conclusion, the relationships between the immune and bone cell populations suggest that they function as an entire regulatory system. This consideration provides a framework for the development of new therapeutic targets for the treatment of bone and immune system disorders.