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.
Highlights
Bone-resorbing osteoclasts (OCLs) were first described 150 years ago [1]
OCLs have been extensively studied to decipher the mechanisms of bone resorption leading to the identification of key factors required for OCL differentiation, fusion, bone adhesion and bone degradation activity
This study elegantly demonstrated for the first time that OCLs involved in fetal bone formation and tooth eruption are originating from the same progenitors as tissue Mφs and differ thereby from OCLs arising in adults (Figures 2A,B) [38, 49]
Summary
Bone-resorbing osteoclasts (OCLs) were first described 150 years ago [1]. Their origin remained unclear for nearly 100 years before they were formally identified as cells of hematopoietic origin. The monocytic origin of OCLs was first demonstrated in colony assays of bone marrow cell fractions [3] From this moment, OCLs have been extensively studied to decipher the mechanisms of bone resorption leading to the identification of key factors required for OCL differentiation, fusion, bone adhesion and bone degradation activity. The immune face of OCLs emerged only 10 years ago when costimulatory signals mediated by ITAM motifs involved in immune cell activation were shown to be essential for OCL differentiation [10,11,12] This was further emphasized by the identification of the important link between DCs and OCLs through the ability of DCs to differentiate into bone-resorbing OCLs under pathological conditions [13, 14] (Table 1). This review addresses the state-of-the-art of this novel vision of the OCL not just as a bone-resorbing cell and as a cell having immune capacities
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