Is rheumatoid arthritis premature osteoarthritis with fetal-like healing?
Rheumatoid arthritis is now known to share many pathogenetic features with osteoarthritis including synovial activation with release of pro-inflammatory cytokines into the synovial fluid. As premature chondrocyte aging and dedifferentiation is increasingly accepted as integral to OA pathogenesis, premature aging of chondrocytes and perhaps subchondral bone may underlie RA. This hypothesis explains many otherwise enigmatic features of RA joint pathology such as the homing of pannus to cartilage. In addition, the surprising finding of mesenchymal precursor cells in RA joints has led to speculation that some aspect of RA pathogenesis involves an attempt to recapitulate the embryonic limb development program. In its totality, RA seems to consist of an attempt to regenerate damaged cartilage and subchondral bone in an adult organism. Since this is impossible, the best the pannus can do is to crawl through empty cartilage lacunae and replace the cartilage and subchondral bone with scar tissue. As opposed to fetal healing, inflammation is necessary to sustain and control the fibroproliferation. Two recently-discovered blood cell types seem to maintain and regulate fibroplastic states in humans: (1) CD34+ and/or monocytoid stem-cell precursors replace aging mesenchymal cells, and (2) regulatory-type adherent CD4+CD28-T cells control growth of those increasingly apoptosis-resistant mesenchymal cells. Such cells occur at multiple sites in AID patients.
Reines
Brandon P
BP
T-cell Tolerance and Memory Section, Laboratory of Cellular and Molecular Immunology, NIAID, NIH, 4 Center Drive, Rm. 111, Bethesda, MD 20892, USA. breines@niaid.nih.gov
D000375:Aging; D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology*; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018448:Models, Immunological; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
D018952:Antigens, CD34; D018106:CD28 Antigens; D015704:CD4 Antigens