Production of parathyroid hormone-related peptide by synovial fibroblasts in human osteoarthritis.
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-1alpha, IL-1beta, IL-6 and TNF-alpha, 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.
Yoshida
T
T
Department of Clinical Chemistry, Hoshi College of Pharmacy, Tokyo, Japan.
Horiuchi
T
T
Sakamoto
H
H
Inoue
H
H
Takayanagi
H
H
Nishikawa
T
T
Yamamoto
S
S
Koshihara
Y
Y
D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology* / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007700:Kinetics; D010003:Osteoarthritis / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D011994:Recombinant Proteins / Q000494:pharmacology; D013583:Synovial Membrane / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate