title: Bone as a Target Organ in Rheumatic Disease: Impact on Osteoclasts and Osteoblasts.
abstract: Dysregulated bone remodeling occurs when there is an imbalance between bone resorption and bone formation. In rheumatic diseases, including rheumatoid arthritis (RA) and seronegative spondyloarthritis, systemic and local factors disrupt the process of physiologic bone remodeling. Depending upon the local microenvironment, cell types, and local mechanical forces, inflammation results in very different effects on bone, promoting bone loss in the joints and in periarticular and systemic bone in RA and driving bone formation at enthesial and periosteal sites in diseases such as ankylosing spondylitis (AS), included within the classification of axial spondyloarthritis. There has been a great deal of interest in the role of osteoclasts in these processes and much has been learned over the past decade about osteoclast differentiation and function. It is now appreciated that osteoblast-mediated bone formation is also inhibited in the RA joint, limiting the repair of erosions. In contrast, osteoblasts function to produce new bone in AS. The Wnt and BMP signaling pathways have emerged as critical in the regulation of osteoblast function and the outcome for bone in rheumatic diseases, and these pathways have been implicated in both bone loss in RA and bone formation in AS. These pathways provide potential novel approaches for therapeutic intervention in diseases in which inflammation impacts bone.
authors.affiliation: Department of Medicine and Division of Rheumatology, University of Massachusetts Medical School, Lazare Research Building Suite 223, 364 Plantation Street, Worcester, MA, 01605, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Baum
authors.affiliation: Department of Medicine and Division of Rheumatology, University of Massachusetts Medical School, Lazare Research Building Suite 223, 364 Plantation Street, Worcester, MA, 01605, USA. ellen.gravallese@umassmed.edu.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Gravallese
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001323:Autoantibodies / Q000276:immunology; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D016723:Bone Remodeling; D001862:Bone Resorption / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism*; D010012:Osteogenesis; D012216:Rheumatic Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D060449:Wnt Signaling Pathway
chemical_list: D001323:Autoantibodies; D019485:Bone Morphogenetic Proteins; D035683:MicroRNAs
keywords: Ankylosing spondylitis; Bone erosions; Bone formation; Bone remodeling; DKK1; Entheses; IL-23; Inflammation; Osteoblast; Osteoclast; Rheumatoid arthritis; Sclerostin; Wnt; microRNAs