The influence of Vitamin D metabolites on the calcification of cartilage matrix and the C-propeptide of type II collagen (Chondrocalcin)

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Abstract
The influence of vitamin D metabolites (at 1 × 10−10 M) on the calcification of cartilage matrix (measured by 45Ca2+ uptake) and the C-propeptide of type II collagen (measured by radioimmunoassay) has been studied using organ cultures and chondrocytes isolated from growth plates of vitamin D-deficient and -sufficient 11-day-old rats. Vitamin D-deficient rats had reduced amounts of C-propeptide in their serum and freshly isolated growth plate chondrocytes. In all chondrocytes cultured from vitamin D-deficient animals, the C-propeptide content was maximal at 24 hr whereas calcification continued to increase for up to 72 hr. In organ and chondrocyte cultures of tissue from vitamin D-sufficient rats, both 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and 24,25-dihydroxycholecalciferol (24,25(OH)2D3) were required for maximal stimulation of calcification and maximal increases in C-propeptide content. In these D-replete tissues, 24,25-(OH)2D3 had a less stimulatory effect on both calcification (organ and cell cultures) and C-propeptide (organ cultures only), while 1,25(OH)2D3 alone had no effect in cell cultures but an inhibitory effect in organ cultures. In all of these studies, maximal stimulation by vitamin D metabolites of 45Ca2+ incorporation was always accompanied by a maximal net increase in CPII content. Since increases were often quantitatively and temporally different, if would appear that the C-propeptide does not simply accumulate by a process of passive binding to mineral but that its increased concentration is the result of an active process that may be causally related to calcification. These observations clearly demonstrate that 24,25(OH)2D3 is alone required for maximal calcification of cartilage matrix in growth plate cartilages of vitamin D-deficient rats and that this metabolite also produces maximal increases in the synthesis of the C-propeptide. Moreover, 1,25(OH)2D3 is required with 24,25(OH)2D3 for the maximal calcification and maximal increases in the amount of C-propeptide which are observed in vitamin D-sufficient animals.
Funding Information
  • Shriners of North America and the Medical Research Council of Canada