Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
The Calcitonin Receptor Is Localized to Specific Phenotypes of Cartilage Chondrocytes In Situ.
Chen-An, Pingping, Li, Yadong, C. Sondergaard, Bodil, Silvestra-Segovia, Toni, Qvist, Per, A. Karsdal, Morten, C. Bay-Jensen, Anne
Arthritis is associated with excessive cartilage loss. Salmon calcitonin is reported to have chondro-protective effect on degenerative joint disease. We have recently shown that the calcitonin receptor (CTR) was expressed by primary chondrocytes; however it was also evident that not all chondrocytes expresses the CTR. Articular cartilage can be divided into different zonal layer, which encumbers different chondrocyte phenotypes; the superficial layerdiscoid chondrocytes, the upper zonespherical chondrocytes, mid zoneresting chondrocytes, deep zonehypertrophic chondrocytes, calcified cartilage and subchondral bone. We therefore investigated, which of these chondrocytes express the CTR in situ.
Full-depth articular cartilage tissue was isolated from the tibia plateau of 20 different patients undergoing total knee replacement. The tissue was fixed, decalcified and embedded in paraffin. Sections of 5 mm were cut, blocked for unspecific binding and stained for the calcitonin receptor using the monoclonal antibody MAb 31/01-1H10 (Welcome receptor, Australia). Dako envision+ system was used for visualization of the antibody binding. Adjacent sections were stained with proteoglycans using safranin O and fast green staining. Sections were evaluated by Mankin score and specific arthritic features were identified in the cartilage. Anotations on positive staining were made of these features. Statistics were performed by Fishers' exact test.
All sections had some degree of pathological features ranging from Mankin score 4 to 10. No or limited immune-reactivity was observed in the discoid chondrocytes of the superficial zone and spherical chondrocytes of the upper zone. In contrast when the superficial zone was lost a fraction of the spherical chondrocytes, namely those with clonal activity, displayed the receptor. At no time did we observe the CTR in the mid zone. Furthermore, we found the receptor to be present in a portion of hypertrophic chondrocytes of the deep zone. These observed distributions were significant (p<0.05). Furthermore, strong proteoglycan staining (intense red staining) was seen in the CTR positive anotations. Since we only observed immune-reactivity in cells with high metabolic activity, assessed by proteoglycan staining and general morphology, and did not observe any staining in the mid zone chondrocytes, it might indicated that the expression of the CTR is related to chondrocytes with high metabolic activity.
We here report that human articular cartilage chondrocytes do express the CTR in situ, and that this expression is associated with chondrocytes with high metabolic activity. The presence of the CTR suggests that chondrocytes are target for treatment with salmon calcitonin. These data support previous data that identifies the expression of CTR in primary osteoarthritic chondrocytes.
To cite this abstract, please use the following information:
Chen-An, Pingping, Li, Yadong, C. Sondergaard, Bodil, Silvestra-Segovia, Toni, Qvist, Per, A. Karsdal, Morten, et al; The Calcitonin Receptor Is Localized to Specific Phenotypes of Cartilage Chondrocytes In Situ. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1500