Synovium as a source of increased amino-terminal parathyroid hormone-related protein expression in rheumatoid arthritis. A possible role for locally produced parathyroid hormone-related protein in the pathogenesis of rheumatoid arthritis
| Autor: | L. A. Cordaro, J. B. Benjamin, Janet L. Funk, D. E. Yocum, Hongbing Wei |
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| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
musculoskeletal diseases
medicine.medical_specialty Parathyroid hormone Pannus Gene Expression Bone resorption Dexamethasone Proinflammatory cytokine Arthritis Rheumatoid Interferon-gamma Internal medicine Osteoarthritis medicine Humans RNA Messenger Glucocorticoids Cells Cultured Receptor Parathyroid Hormone Type 1 Parathyroid hormone-related protein business.industry Interleukin-6 Cartilage Synovial Membrane Parathyroid Hormone-Related Protein Proteins General Medicine medicine.disease musculoskeletal system Immunohistochemistry Endocrinology medicine.anatomical_structure Parathyroid Hormone Receptors Parathyroid Hormone Tumor necrosis factor alpha Synovial membrane business hormones hormone substitutes and hormone antagonists Research Article Interleukin-1 |
| Popis: | Proinflammatory cytokines, including tumor necrosis factor (TNF) and interleukin 1 (IL-1), mediate the joint destruction that characterizes rheumatoid arthritis (RA). Previous studies have shown that parathyroid hormone-related protein (PTHrP) is a member of the cascade of proinflammatory cytokines induced in parenchymal organs during lethal endotoxemia. To test the hypothesis that NH2-terminal PTHrP, a potent bone resorbing agent, could also be a member of the synovial cascade of tissue-destructive cytokines whose expression is induced in RA, PTHrP expression was examined in synovium and synoviocytes obtained from patients with RA and osteoarthritis (OA). PTHrP production, as determined by measurement of immunoreactive PTHrP(1-86) in tissue explant supernatants, was increased 10-fold in RA versus OA synovial tissue. Synovial lining cells and fibroblast-like cells within the pannus expressed both PTHrP and the PTH/PTHrP receptor, findings that were confirmed by in vitro studies of cultured synoviocytes. TNF-alpha and IL-1beta stimulated PTHrP expression in synoviocytes, while dexamethasone and interferon-gamma, agents with some therapeutic efficacy in the treatment of RA, inhibited PTHrP release. Treatment of synoviocytes with PTHrP(1-34) stimulated IL-6 secretion. These results suggest that proinflammatory cytokine-stimulated production of NH2-terminal PTHrP by synovial tissue directly invading cartilage and bone in RA may mediate joint destruction through direct effects on cartilage or bone, or, indirectly, via the induction of mediators of bone resorption in the tumor-like synovium. |
| Databáze: | OpenAIRE |
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