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Histopathology of Bone Erosions in Rheumatoid Arthritis

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Focal bone erosions in areas of pannus invasion are a hallmark of established rheumatoid arthritis (RA). We have utilized histochemical techniques and in situ hybridization to demonstrate that the cells responsible for these bone erosions express an osteoclast phenotype. Our results indicate that the multinucleated cells in resorption lacunae in continuity with pannus express abundant tartrate resistant acid phosphatase (TRAP), cathepsin K and calcitonin receptor (CTR) mRNA. Although CTR expression is restricted to multinucleated and mononuclear cells on the mineralized tissue surfaces, numerous TRAP positive mono- and multinucleated cells are present within the pannus remote from bone surfaces. We speculate that these TRAP positive cells represent osteoclast precursors that are recruited to the pannus tissue. Interaction of these cells with bone and calcified cartilage provides the additional signals that induce these cells to differentiate into resorbing cells with a definitive osteoclast phenotype. To further investigate the specific factors involved in the differentiation of osteoclasts in RA we have initiated studies to examine the expression of a recently described regulator of osteoclastogenesis, osteoclast differentiation factor (ODF), a member of the membrane associated TNF-ligand family, and its putative receptor on osteoclast precursors, the receptor activator of NF-κB (RANK). Analysis of synovial tissues by RT-PCR from eight patients with RA, five with juvenile arthritis and three with normal synovium reveals the expression of mRNA for ODF in 7/8 RA, 5/5 juvenile arthritis, and 0/3 normal cases. These data provide preliminary evidence that ODF may be an important factor in the pathogenesis of osteoclast-mediated bone resorption in RA.


  1. Gravallese EM, Harada Y, Wang JT, Thornhill TS, Juppner H, Goldring SR: Identification of cell types responsible for bone resorption in rheumatoid arthritis and juvenile rheumatoid arhtritis. Am J Path. 1998, 152: 943-951.

    PubMed  CAS  PubMed Central  Google Scholar 

  2. Darling JM, Goldring SR, Harada Y, Handel ML, Glowacki J, Gravallese EM: Multinucleated cells in pigmented villonodular synovitis and giant cell tumor of tendon sheath express features of osteoclasts. Am J Path. 1997, 150: 1383-1394.

    PubMed  CAS  PubMed Central  Google Scholar 

  3. Gravallese EM, Handel ML: Synovial tissue analysis in rheumatoid arthritis. In UpToDate. Edited by Rose BD. Wellesley MA: UpToDate. 1998

    Google Scholar 

  4. Suda T, Nakamura I, Jimi E, Takahashi N: Regulation of osteoclast function. J Bone Miner Res. 1997, 12: 869-879.

    Article  PubMed  CAS  Google Scholar 

  5. Goldring SR, Polisson RP: Bone disease in rheumatological disorders. In Metabolic Bone Disease, Second Edition. Edited by Avioli L and Krane SM. San Diego: Academic Press. 1998, 621-635.

    Google Scholar 

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Gravallese, E., Manning, C., Tsay, A. et al. Histopathology of Bone Erosions in Rheumatoid Arthritis. Arthritis Res Ther 1 (Suppl 1), S37 (1999).

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