ABSTRACT
OBJECTIVES: The aim of this study was to describe expression of parathyroid hormone-related peptide (PTHrP) in collagen-induced arthritis (CIA), a well-established animal model for rheumatoid arthritis. METHODS: CIA was induced in female dark agouti rats. Inguinal (ILNs) and popliteal (PLNs) lymph nodes and distal interphalangeal joints (DIP) were retrieved at different time points. Tissues were processed for detection of PTHrP and cell marker proteins by immunohistochemistry. Lymph node RNA was extracted, and PTHrP mRNA quantified using competitive reverse transcriptase polymerase chain reaction. RESULTS: Hyperplasia of ILNs was observed 2 days after injection, coinciding with the peak in PTHrP expression in ILNs (1240 +/- 373 gene copies/ng RNA vs normal 339 +/- 120, P < 0.05). Hyperplasia of PLNs was first seen at 1 day after onset of arthritis, coinciding with the peak in PTHrP expression in PLNs (2267 +/- 697 vs normal 781 +/- 136, P < 0.01). PTHrP expression in PLNs remained increased 5 days after onset (1361 +/- 302 vs normal 781 +/- 136, P < 0.05). In both PLNs and ILNs PTHrP protein was localized to high endothelial venules, lymphocytes and monocytes/macrophages. In DIP joint synovium PTHrP staining was first detected on day 10 after onset, and was most abundant at day 20 after onset, at sites of bone resorption and deposition, where it was localized to neutrophils, cells of monocyte lineage and osteoblasts. CONCLUSIONS: Changes in ILN and PLN PTHrP mRNA expression suggest that elevated levels of the cytokine are associated with aggravation of the inflammatory immune response. Changes in PTHrP in DIP joints indicate its involvement in late rather than early pathogenic events in CIA joints.
