Immune Function and Diversity of Osteoclasts in Normal and Pathological Conditions

Abstract

Osteoclasts (OCLs) are key players in controlling bone remodeling. Modifications in their differentiation or bone resorbing activity are associated with a number of pathologies ranging from osteopetrosis to osteoporosis, chronic inflammation and cancer, that are all characterized by immunological alterations. Therefore, the 2000s were marked by the emergence of osteoimmunology and by a growing number of studies focused on the control of OCL differentiation and function by the immune system. At the same time, it was discovered that OCLs are much more than bone resorbing cells. As monocytic lineage-derived cells, they belong to a family of cells that displays a wide heterogeneity and plasticity and that is involved in phagocytosis and innate immune responses. However, while OCLs have been extensively studied for their bone resorption capacity, their implication as immune cells was neglected for a long time. In recent years, new evidence pointed out that OCLs play important roles in the modulation of immune responses toward immune suppression or inflammation. They unlocked their capacity to modulate T cell activation, to efficiently process and present antigens as well as their ability to activate T cell responses in an antigen-dependent manner. Moreover, similar to other monocytic lineage cells such as macrophages, monocytes and dendritic cells, OCLs display a phenotypic and functional plasticity participating to their anti-inflammatory or pro-inflammatory effect depending on their cell origin and environment. This review will address this novel vision of the OCL, not only as a phagocyte specialized in bone resorption, but also as innate immune cell participating in the control of immune responses.

Friend or Foe? Essential Roles of Osteoclast in Maintaining Skeletal Health

“…OCs, the unique bone-resorbing cells, arise from HSCs and belong to the monocytic family [21,32]. In the activation phase of bone remodeling, mononuclear OC precursors in the bone marrow or from blood circulation are attracted to prospective resorption sites, where they attach to the matrix surface and further differentiate into mature OCs (giant multinucleated cells) via cell fusion, termed as "multinucleation" [5,[32][33][34].…”

“…rough cell-cell contact, cell-bone matrix interaction, and paracrine factors, OCs have crosstalk with other bone cells, stem cells, and immune cells in the bone microenvironment, which affects recruitment, differentiation, and function of not only themselves but also the other cells [19][20][21]. is effect of OCs on other cells is more apparent during skeletal aging due to deteriorations on mesenchymal stem cell/ mesenchymal stromal cell-(MSC-) derived osteogenesis and chondrogenesis, while HSC-derived osteoclastogenesis advances with increasing age, thereby gaining the initiative in the bone remodeling process and functioning predominantly over other factors [22][23][24][25].…”

Does Allergy Break Bones? Osteoporosis and Its Connection to Allergy

“…Osteoclasts despite their heterogeneity in origin and environment are considered a single population of cells to be regarded as having immune capacities in addition to the well-known bone-resorbing role. This new vision of osteoclasts recognizes their leading role in the regulation of the bone immune status both in the steady state and during inflammatory processes [15]. The fact that osteoblasts can influence the myeloid lineage in the progression of preneoplastic and neoplastic transformations represents another strong connection between the immune system and bone [16].…”

scSTATseq: Diminishing Technical Dropout Enables Core Transcriptome Recovery and Comprehensive Single-cell Trajectory Mapping

“…We next sought to exploit these advantages of scSTATseq to investigate a dynamic process that could be modeled using RAW cells, namely osteoclast differentiation. Although osteoclasts are a primary pathogenic cell type contributing to osteoporosis, the molecular mechanisms underlying their differentiation remain incompletely understood, and may be of interest for therapeutic development 14,15,16 . Sequencing of RANKL-stimulated RAW cells at 4 time points revealed a similar set of genes recovered and low dropout rates across all samples ( Fig S7), with clear time-dependent changes in the expression of a number of factors previously associated with osteoclast differentiation ( Fig 3A).…”