title: Alternative pathways of osteoclastogenesis in inflammatory arthritis.
abstract: Osteoclasts are cells of haematopoietic origin that are uniquely specialized to degrade bone. Under physiological conditions, the osteoclastogenesis pathway depends on macrophage colony-stimulating factor 1 (CSF-1, also known as M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). However, an emerging hypothesis is that alternative pathways of osteoclast generation might be active during inflammatory arthritis. In this Perspectives article, we summarize the physiological pathway of osteoclastogenesis and then focus on experimental findings that support the hypothesis that infiltrating inflammatory cells and the cytokine milieu provide multiple routes to bone destruction. The precise identity of osteoclast precursor(s) is not yet known. We propose that myeloid cell differentiation during inflammation could be an important contributor to the differentiation of osteoclast populations and their associated pathologies. Understanding the dynamics of osteoclast differentiation in inflammatory arthritis is crucial for the development of therapeutic strategies for inflammatory joint disease in children and adults.
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California, Shriners Hospitals for Children Northern California, 2425 Stockton Boulevard, Room 653A, Sacramento, CA 95817, USA.
authors.forename: Iannis E
authors.initials: IE
authors.lastname: Adamopoulos
authors.affiliation: Division of Pediatric Rheumatology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Mellins
mesh_terms: D000818:Animals; D001168:Arthritis / Q000473:pathology*; D001862:Bone Resorption; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D010010:Osteoclasts / Q000473:pathology*