Learning from Monocyte-Macrophage Fusion and Multinucleation: Potential Therapeutic Targets for Osteoporosis and Rheumatoid Arthritis.
Excessive bone resorption by osteoclasts (OCs) covers an essential role in developing bone diseases, such as osteoporosis (OP) and rheumatoid arthritis (RA). Monocytes or macrophages fusion and multinucleation (M-FM) are key processes for generating multinucleated mature cells with essential roles in bone remodelling. Depending on the phenotypic heterogeneity of monocyte/macrophage precursors and the extracellular milieu, two distinct morphological and functional cell types can arise mature OCs and giant cells (GCs). Despite their biological relevance in several physiological and pathological responses, many gaps exist in our understanding of their formation and role in bone, including the molecular determinants of cell fusion and multinucleation. Here, we outline fusogenic molecules during M-FM involved in OCs and GCs formation in healthy conditions and during OP and RA. Moreover, we discuss the impact of the inflammatory milieu on modulating macrophages phenotype and their differentiation towards mature cells. Methodological approach envisaged searches on Scopus, Web of Science Core Collection, and EMBASE databases to select relevant studies on M-FM, osteoclastogenesis, inflammation, OP, and RA. This review intends to give a state-of-the-art description of mechanisms beyond osteoclastogenesis and M-FM, with a focus on OP and RA, and to highlight potential biological therapeutic targets to prevent extreme bone loss.
['Gambari|Laura|L|0000-0001-8126-5040', 'Grassi|Francesco|F|0000-0002-5127-9561', 'Roseti|Livia|L|0000-0001-5760-3791', 'Grigolo|Brunella|B|0000-0002-3990-6745', 'Desando|Giovanna|G|0000-0003-3338-5747']
D000818:Animals D001172:Arthritis, Rheumatoid D001857:Bone Matrix D001862:Bone Resorption D002459:Cell Fusion D004164:Diphosphonates D015870:Gene Expression D015726:Giant Cells D006801:Humans D008264:Macrophages D009000:Monocytes D010010:Osteoclasts D010012:Osteogenesis D010024:Osteoporosis
osteoporosis rheumatoid arthritis osteoclasts macrophage fusion and multinucleation giant cells inflammation bone loss macrophage polarisation natural compounds