The inhibitory effect of salmon calcitonin on tri-iodothyronine induction of early hypertrophy in articular cartilage.

Abstract

OBJECTIVE:

Salmon calcitonin has chondroprotective effect both in vitro and in vivo, and is therefore being tested as a candidate drug for cartilage degenerative diseases. Recent studies have indicated that different chondrocyte phenotypes may express the calcitonin receptor (CTR) differentially. We tested for the presence of the CTR in chondrocytes from tri-iodothyronin (T3)-induced bovine articular cartilage explants. Moreover, investigated the effects of human and salmon calcitonin on the explants.

METHODS:

Early chondrocyte hypertrophy was induced in bovine articular cartilage explants by stimulation over four days with 20 ng/mL T3. The degree of hypertrophy was investigated by molecular markers of hypertrophy (ALP, IHH, COLX and MMP13), by biochemical markers of cartilage turnover (C2M, P2NP and AGNxII) and histology. The expression of the CTR was detected by qPCR and immunohistochemistry. T3-induced explants were treated with salmon or human calcitonin. Calcitonin down-stream signaling was measured by levels of cAMP, and by the molecular markers.

RESULTS:

Compared with untreated control explants, T3 induction increased expression of the hypertrophic markers (p<0.05), of cartilage turnover (p<0.05), and of CTR (p<0.01). Salmon, but not human, calcitonin induced cAMP release (p<0.001). Salmon calcitonin also inhibited expression of markers of hypertrophy and cartilage turnover (p<0.05).

CONCLUSIONS:

T3 induced early hypertrophy of chondrocytes, which showed an elevated expression of the CTR and was thus a target for salmon calcitonin. Molecular marker levels indicated salmon, but not human, calcitonin protected the cartilage from hypertrophy. These results confirm that salmon calcitonin is able to modulate the CTR and thus have chondroprotective effects.

• Authors: Pingping Chen-An, Kim Vietz Andreassen, Kim Henriksen, Yadong Li, Morten Asser Karsdal, Anne-Christine Bay-Jensen
• Journal: PloS one (PLoS One) Vol. 7 Issue 6 Pg. e40081 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22768225 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Receptors, Calcitonin
• Triiodothyronine
• salmon calcitonin
• Calcitonin
• Cyclic AMP

Topics

• Animals
• Biomarkers (metabolism)
• Calcitonin (pharmacology)
• Cartilage, Articular (drug effects, metabolism, pathology)
• Cattle
• Chondrocytes (drug effects, metabolism, pathology)
• Cyclic AMP (metabolism)
• Extracellular Space (drug effects, metabolism)
• Humans
• Hypertrophy
• Protein Transport (drug effects)
• Receptors, Calcitonin (metabolism)
• Triiodothyronine (administration & dosage, pharmacology)