Production of parathyroid hormone‐related peptide by synovial fibroblasts in human osteoarthritis

Abstract
Synovial fibroblasts from patients with osteoarthritis in culture produced parathyroid hormone‐related peptide (PTHrP) on treatment with phorbol ester (TPA) in a dose‐ and time‐dependent manner. The levels of PTHrP immunoreactivity in the conditioned medium of synovial fibroblast cultures were measured using specific PTHrP antibody. The maximum production was obtained at a concentration of 10−8 M and 24 h after TPA treatment. But sensitivity to TPA of synovial fibroblasts differed among four patients from slight to marked. PTHrP production was also induced with inflammatory cytokines, such as 1 ng/ml of IL‐1α, IL‐1β, IL‐6 and TNF‐α, and 10−6 M prostaglandin E2, after 24 h treatment. The expression of PTHrP was confirmed by reverse‐transcriptase polymerase chain reaction. Since the synovial fibroblasts isolated from osteoarthritic patients produce high levels of IL‐6 and IL‐8, typical cytokines produced in synovial fibroblasts, production of PTHrP may provide new insight into the pathophysiology of joint disorder.

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