Additive effects of acidosis and parathyroid hormone on mouse osteoblastic and osteoclastic function.
Patients with end-stage renal disease are acidotic and often develop secondary hyperparathyroidism. Whether acidosis contributes to the bone disease observed in these patients is not clear. To determine whether acidosis and parathyroid hormone (PTH) have additive effects on net calcium efflux (JCa+) from bone and on bone cell function, we measured JCa+, osteoblastic collagen synthesis, and osteoclastic beta-glucuronidase release from neonatal mouse calvariae cultured in control (Ctl, pH approximately 7.4) or acidified (Met, pH approximately 7.1) medium with or without a submaximal concentration of PTH (10(-10) M) for 48 h. Compared with Ctl, from 24 to 48 h JCa+ was increased with Met and with PTH, and the combination of Met + PTH increased JCa+ further. Compared with Ctl, collagen synthesis was decreased with Met and with PTH and decreased further with Met + PTH. There was an inverse correlation between percent collagen synthesis and JCa+. Compared with Ctl, beta-glucuronidase release into the medium was increased with Met and with PTH and increased further with Met + PTH. There was a direct correlation between medium beta-glucuronidase activity and JCa+. Osteoclastic beta-glucuronidase activity correlated inversely with osteoblastic collagen synthesis. During cultures to 96 h, there continued to be greater JCa+ from calvariae incubated with Met + PTH than from those with either treatment alone. Thus acidosis and PTH independently stimulated JCa+ from bone, inhibited osteoblastic collagen synthesis, and stimulated osteoclastic beta-glucuronidase secretion, whereas the combination had a greater effect on each of these parameters than either treatment alone. These findings indicate that acidosis and PTH can have an additive effect on bone cell function and suggest that uremic osteodystrophy may result from a combination of a low pH and an elevated PTH.
Bushinsky
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DA
Nephrology Unit, University of Rochester School of Medicine and Dentristry, New York 14642, USA.
Nilsson
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EL
D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000096:biosynthesis; D005966:Glucuronidase / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D010006:Osteoblasts / Q000187:drug effects* / Q000502:physiology*; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D013997:Time Factors
D010281:Parathyroid Hormone; D003094:Collagen; D005966:Glucuronidase; D002118:Calcium