Metabolic acidosis up-regulates PTH/PTHrP receptors in UMR 106-01 osteoblast-like cells.
BACKGROUND
Metabolic acidosis results in skeletal demineralization by multiple mechanisms. One of these involves the inorganic phase of bone by which hydrogen ion is buffered by bone carbonate. In addition, the cellular components of bone participate by the induction and repression of several skeletal genes. Previous studies have suggested that the action of parathyroid hormone (PTH), a major regulator of bone turnover, might be altered by acidosis. The present studies were designed to test directly, in vitro, whether acidosis altered the effects of PTH in UMR 106-01 osteoblast-like cells.


METHODS
Studies were conducted in confluent cultures of UMR 106-01 cells in modified Eagle's medium (MEM) with 5% fetal bovine serum (FBS) at pH values varying from 7.4 to 7.1 by addition of HCl. After time periods of 4 to 48 hours, cells were tested for cyclic AMP generation in response to PTH. PTH binding and PTH/PTHrP receptor mRNA levels were determined by radioligand binding assay and Northern analysis respectively.


RESULTS
After 48 hours, decreases in pH from 7.4 to 7.1 resulted in a progressive increase in PTH-stimulated cyclic-AMP generation from 1978 +/- 294 to 4968 +/- 929 pmol/culture/5 min (P < 0.05). Basal cyclic AMP concentrations were unchanged. PTH binding increased 1.5- to twofold. Competitive inhibition binding revealed an increase in receptor number supported by up-regulation of PTH/PTHrP receptor mRNA up to twofold from control levels.


CONCLUSIONS
These findings demonstrate that metabolic acidosis stimulates the response to PTH in UMR 106-01 osteoblast-like cells by a mechanism that involves an increase in the levels of PTH/PTHrP receptor mRNA. Thus, the skeletal response to acidosis that includes an increase in bone resorption may result, at least in part, from an increase in PTH/PTHrP receptors leading to an enhanced effect of PTH on bone.
Disthabanchong
Sinee
S
Division of Nephrology, Saint Louis University, 3635 Vista Avenue, St. Louis, MO 63110, USA.
Martin
Kevin J
KJ
McConkey
Charles L
CL
Gonzalez
Esther A
EA
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D012516:Osteosarcoma; D010281:Parathyroid Hormone / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein; D036361:Peptide Hormones / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D018016:Receptors, Parathyroid Hormone / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D036361:Peptide Hormones; D012333:RNA, Messenger; D018016:Receptors, Parathyroid Hormone; D000242:Cyclic AMP