EFFECTS OF CALCITONIN AND PARATHYROID-HORMONE ON CALCIFICATION OF PRIMARY CULTURES OF CHICKEN GROWTH-PLATE CHONDROCYTES

Few studies have been directed toward elucidating the action of calcit onin (CT) and parathyroid hormone (PLH) on growth plate chondrocytes, cells directly involved in longitudinal bone growth and provisional ca lcification, In this study, primary cultures of avian growth plate cho ndrocytes that calcify without the supplement of beta-glycerophosphate were used to investigate the effects of synthetic human CT and 1-34 b ovine PTH on (1) cell division and growth; (2) the deposition of Ca2and inorganic phosphate (Pi); (3) the activity of alkaline phosphatase (AP), an enzyme long associated with the mineralization process; (4) the levels of proteoglycans; and (5) the synthesis of collagens, Added continually to preconfluent cultures from day 6 until hat-vest, CT (1 -30 nM) and PTH (0.1-1.0 nM) increased mineral deposition; the maximal increase was seen between days 18-21 at 10 nM CT (175-260%) and 0.5 n M PTH (similar to 170-280%), both p < 0.001, er had no significant eff ect on cellular protein, or AP-specific activity, whereas PTH increase d cellular protein, DNA, proteoglycan, and collagen content of the cul tures in a dosage-dependent manner, AP activity and levels of Type II and X collagens and fibronectin in the culture medium showed a biphasi c response to PTH; maximal increases were seen at 0.5 nM between days 15-18, Longer exposure (days 21-27) to PTH at higher levels (5-10 nM) caused a marked decrease in AP activity but: a lesser decrease in the collagens, These results indicate that CT and PTH can act directly on chondrocytes to stimulate mineralization, but that PTH specifically st imulated cell division and synthesis of cellular and extracellular pro teins by growth plate chondrocytes, The implications of these findings with regard to Ca2+ homeostasis and bone formation are discussed.