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. 2004 Aug;63(8):917–922. doi: 10.1136/ard.2003.008904

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

E Gomez-Barrena 1, O Sanchez-Pernaute 1, R Largo 1, E Calvo 1, P Esbrit 1, G Herrero-Beaumont 1
PMCID: PMC1755102  PMID: 15249318

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.

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Figure 1.

Figure 1

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 PTHrP immunostaining with anti-PTHrP antiserum C13 in representative sections of medial femoral condyle from either a normal rabbit (A, B), or rabbits with early OA (C, D) or AIA cartilage (E, F). Original magnifications: x100 (A, C, E); x400 (B); x200 (D, F).

Figure 2.

Figure 2

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 PTHrP immunostaining with antiserum C13 in representative sections of medial femoral condyle from a normal rabbit (A, B), or rabbits with either late OA (C, D) or AIA cartilage (E, F). A decrease in both cell and matrix PTHrP staining, as well as in cell number, was observed in late AIA samples mostly at the superficial (A, C, E), but also at the deep layer (B, D, F) of cartilage. Of note, cell PTHrP positivity in late OA and AIA. Original magnifications: x100 (A, C); x200 (E); x400 (B, D, F).

Figure 5.

Figure 5

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 Crude score values (mean (SD)) for cartilage PTHrP staining in sequential AIA. Comparison with Mann-Whitney test between early AIA and controls (*p<0.05) and between late AIA and controls (†p<0.05; ††p<0.01).

Figure 7.

Figure 7

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 Crude score values (mean (SD)) for cartilage PTHrP staining in AIA and OA compared with controls. Comparison with Mann-Whitney test between AIA cartilage and controls (†p<0.05; ††p<0.01), and between OA cartilage and controls (not significant). Comparisons between AIA and OA cartilage samples are also displayed (*p<0.05; **p<0.01).

Figure 3.

Figure 3

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 PTHrP immunostaining using antiserum C13 in representative sections of medial femoral condyle from OA rabbit cartilage, showing an intense staining in the proliferating cell clones. Original magnifications: x400 (A); x1000 (B).

Figure 4.

Figure 4

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 PCNA cell staining in clones around cartilage degenerative lesions (A). Detailed PCNA positive cell (B). Original magnifications: x400 (A); x1000 (B).

Figure 6.

Figure 6

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 Crude score values (mean (SD)) for cartilage PTHrP staining in sequential OA. Comparison with Mann-Whitney test between early OA and controls, and between late OA and controls. Note that no significant differences were found in the crude variables.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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