Sequential changes of parathyroid hormone related protein (PTHrP) in articular cartilage during progression of inflammatory and degenerative arthritis

Abstract

Objective: To investigate immunolocalisation of parathyroid hormone related protein (PTHrP) in two sequential models of experimental cartilage damage (inflammatory and degenerative) in order to elucidate differences in chondrocyte response to the disease. Methods: Immunohistochemistry with a polyclonal rabbit antiserum to the N-terminal domain of PTHrP was used to detect this protein in two different rabbit models sharing progressive cartilage damage: antigen induced arthritis (AIA) and osteoarthritis (OA) secondary to partial medial meniscectomy. Cartilage specimens from early (2 days in AIA; 8 weeks in experimental OA) and late (3 weeks in AIA; 52 weeks in OA) disease were compared. Results: Cell and matrix PTHrP staining in early AIA and OA was similar to that in controls. Late AIA cartilage showed a significant decrease in PTHrP positive cells and in the cartilage matrix. In contrast, at late OA stages, distinct PTHrP positivity was detected in proliferating cell clones, as assessed by proliferating cell nuclear antigen staining around cartilage damaged areas. Conclusion: PTHrP staining of hyaline articular cartilage shows a different pattern during progression of each type of arthritis: an overall decrease associated with the inflammatory disease, and an increase in the proliferating chondrocyte clones with degenerative arthritis.

PTHrP overexpression partially inhibits a mechanical strain-induced arthritic phenotype in chondrocytes

“…Additionally, high magnitude CTS was discovered to increase gene expression of Col10a1, a marker of chondrocyte hypertrophy, and this phenomenon may be mediated by Runx2 due to their concurrent increase. Endogenous bPTHrP gene expression increased with CTS, consistent with increased PTHrP secretion seen in human osteoarthritic cartilage38, 39 and thought to be a self-repair response to damaged cartilage40. Interestingly, gene expression of PTH1R, a marker of pre-hypertrophy, decreased initially for the first 12 hours with CTS but steadily increased for the next 36 hours (data not shown).…”

Parathyroid hormone 1–34 inhibits terminal differentiation of human articular chondrocytes and osteoarthritis progression in rats

“…Investigators have found a sequential change of PTHrP localized in articular cartilage during the progression of inflammatory and degenerative arthritis (39). It has been reported that PTHrP(1-40) suppresses T3-induced hypertrophy of articular chondrocytes (40).…”

Association of Polymorphism in Growth and Differentiation Factor 5 Gene With Osteoarthritis Knee

“…aggrecanase ADAMTS-5, cytokines chondrocyte terminal differentiation-related genes and caspase 3 are reported to be upregulated in the vicinity of the lesion (Hardingham et al, 1992;Watanabe et al, 1998;Tetlow et al, 2001;Aigner and Stove, 2003).The most severely damaged rodent knee OA articular cartilage has shown to be significantly associated with reduced expression of proliferationrelated growth factors and their signaling molecules such as PTHrP, TGFβ3 and Smad-2P, TGFβ1 and its receptor II (Gomez-Barrena et al, 2004;Davidson et al, 2006).…”