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Review
. 2012 Jun;64(6):1697-707.
doi: 10.1002/art.34453. Epub 2012 Mar 5.

Osteoarthritis: a disease of the joint as an organ

Richard F Loeser  1 , Steven R Goldring, Carla R Scanzello, Mary B Goldring
Affiliations
Review

Osteoarthritis: a disease of the joint as an organ

Richard F Loeser et al. Arthritis Rheum. 2012 Jun.
No abstract available

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Figures

Figure 1
Figure 1
Sagittal inversion recovery (A–C) and coronal fast spin echo (D–F) images illustrating the magnetic resonance imaging findings of osteoarthritis. (A) reactive synovitis (thick white arrow), (B) subchondral cyst formation (white arrow), (C) bone marrow edema (thin white arrows), (D) partial thickness cartilage wear (thick black arrow), (E–F) full thickness cartilage wear (thin black arrows), subchondral sclerosis (arrowhead) and marginal osteophyte formation (double arrow). Image courtesy of Drs. Hollis Potter and Catherine Hayter, Hospital for Special Surgery, New York, NY
Figure 2
Figure 2
Histologic features of osteoarthritis (OA). The normal synovium has a thin (1–2 cells thick) lining layer and a vascularized, loose connective tissue sublining layer. OA synovium demonstrates features of synovial villous hyperplasia (#), lining hyperplasia (arrows), increased vascularity (+) and perivascular mononuclear cell (inflammatory) infiltration. In OA articular cartilage, loss of cells and matrix is accompanied by areas of cell clusters. There is thickening of the calcified zone and duplication of the tidemark which normally separates articular cartilage from the underlying calcified cartilage. The subchondral bone is also thickened and vascular invasion, which can extend through the tidemark and into the base of the articular cartilage, is seen. Histology kindly provided by Ed DiCarlo, Hospital for Special Surgery, New York, NY.
Figure 3
Figure 3
Selected factors involved in the osteoarthritic process in the synovium, cartilage, and bone. Proteins including S100 proteins (alarmins) and damage-associated molecular pattern molecules (DAMPs), cytokines (interleukin (IL)-1β, tumor necrosis factorα (TNFα), IL-15), chemokines (C-C motif ligand 19 (CCL19), monocyte chemotactic protein-1 (MCP-1), monocyte inflammatory protein (MIP-1β)), and complement components released from the synovium can stimulate articular chondrocytes through activation of various cell surface receptors including toll-like receptors (TLRs), cytokine and chemokine receptors, or by formation of the complement membrane attack complex. Other factors which activate cartilage matrix destruction include binding of native type II collagen to discoidin domain receptor 2 (DDR2), fibronectin fragments to the α5β1 integrin, Wnt proteins to frizzled and binding of extracellular factors to syndecan-4. Syndecan-4 may also act by targeting A Disintegrin and Metalloproteinase with Thrombospondin Motifs-5 (ADAMTS-5) to the cell surface. Various signaling pathways lead to activation of a set of transcription factors that regulate expression of matrix degrading enzymes and inflammatory mediators. Matrix fragments released from the cartilage can stimulate further synovitis. Production of vascular endothelial growth factor (VEGF) in cartilage and bone stimulates vascular invasion from subchondral bone into the zone of calcified cartilage. VEGF, sclerostin, receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), urokinase-type plasminogen activator (uPA), matrix metalloproteinase (MMP)s, IL-6 and IL-8 mediate bone remodeling and potentially diffuse to the cartilage to also promote cartilage matrix destruction. Transforming growth factor-β (TGF-β) and bone morphogenic protein-2 (BMP-2) produced in the synovium, cartilage, and bone stimulate osteophyte formation.
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