IDENTIFICATION OF CELL-TYPES RESPONSIBLE FOR BONE-RESORPTION IN RHEUMATOID-ARTHRITIS AND JUVENILE RHEUMATOID-ARTHRITIS

Focal resorption of bone at the bone-pannus interface is common in rhe umatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) and can result in significant morbidity, However, the specific cellular and h ormonal mechanisms involved in this process are not well established, We examined tissue sections from areas of bone erosion in patients wit h RA and JRA, Multinucleated cells (MNCs) were present in resorption l acunae in areas of calcified cartilage and in subchondral bone immedia tely adjacent to calcified cartilage, as previously described. mRNA fo r the calcitonin receptor (CTR) was localized to these MNCs in bone re sorption lacunae, a finding that definitively identifies these cells a s osteoclasts. These MNCs were also positive for tartrate-resistant ac id phosphatase (TRAP) mRNA and TRAP enzymatic activity, Occasional mon onuclear cells on the bone surface were also CTR positive, Mononuclear cells and MNCs not on bone surfaces were CTR negative, The restrictio n of CTR-positive cells to the surface of mineralized tissues suggests that bone and/or calcified cartilage provide signals that are critica l for the differentiation of hematopoietic osteoclast precursors to fu lly differentiated osteoclasts, Some MNCs and mononuclear cells off bo ne and within invading tissues were TRAP positive. These cells likely represent the precursors of the CTR-TRAP-positive cells on bone, Parat hyroid hormone receptor mRNA was present in cells with the phenotypic appearance of osteoblasts, in close proximity to MNCs, and in occasion al cells within pannus tissue, but not in the MNCs in bone resorption lacunae, These findings demonstrate that osteoclasts within the rheuma toid lesion do not express parathyroid hormone receptor, In conclusion , the resorbing cells in RA exhibit a definitive osteoclastic phenotyp e, suggesting that pharmacological agents that inhibit osteoclast recr uitment or activity are rational targets for blocking focal bone erosi on in patients with RA and JRA.