Synovial Fluids from Patients with Osteoarthritis and Rheumatoid Arthritis Contain High Levels of Parathyroid Hormone–Related Peptide

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  • Hiroaki Kohno
    Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan
  • Chohei Shigeno
    Calcium Laboratory, Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan
  • Ryuichi Kasai
    Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan
  • Haruhiko Akiyama
    Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan
  • Hirokazu Iida
    Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan
  • Tadao Tsuboyama
    Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan
  • Kanji Sato
    Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical College, Tokyo, Japan
  • Junji Konishi
    Calcium Laboratory, Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan
  • Takashi Nakamura
    Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan

書誌事項

公開日
1997-05-01
権利情報
  • https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model
DOI
  • 10.1359/jbmr.1997.12.5.847
公開者
Oxford University Press (OUP)

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<jats:title>Abstract</jats:title> <jats:p>High levels of immunoreactive and biologically active parathyroid hormone–related peptide (PTHrP) were detected in synovial fluids from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). The levels of PTHrP immunoreactivity in synovial fluids, measured by a two-site immunoradiometric assay (IRMA) which detects hPTHrP(1–72) or longer peptides and a radioimmunoassay (RIA) specific to the carboxy-terminal portion of hPTHrP, were 3.2 ± 0.3 pmol of hPTHrP(1–86)/l and 61 ± 7.0 pmol of hPTHrP(109–141)/l in OA patients (mean ± SE, n = 23), and 4.8 ± 0.8 pmol of hPTHrP(1–86)/l and 164 ± 30 pmol of hPTHrP(109–141)/l in RA patients (n = 26). Synovial fluid PTHrP levels distributed above the normal plasma reference ranges in each assay (0.7–2.6 pmol of hPTHrP(1–86)/l; 16–60.6 pmol of hPTHrP(109–141)/l). After concentration using sequential cation-exchange and reverse-phase chromatography, synovial fluid exhibited the activity that stimulated cyclic adenosine monophosphate (cAMP) accumulation in osteoblastic ROS 17/2.8 cells expressing PTH/PTHrP receptors. The cAMP accumulation activity in synovial fluid was sensitive to coincubation with excess hPTHrP(3–40), a PTH/PTHrP receptor antagonist, and was completely neutralized by preincubation with a monoclonal antibody specific to hPTHrP but not PTH. Immunohistochemical analysis of RA synovium revealed that PTHrP was localized in fibroblast-like cells in the synovial pannus invading articular cartilage. Our data show that PTHrP is produced locally by the diseased synovial tissue and released into synovial fluid at high concentrations, allowing us to hypothesize that PTHrP plays a novel role as a paracrine/autocrine factor in the pathology of OA and RA.</jats:p>

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