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Acidosis inhibits bone formation by osteoblasts in vitro by preventing mineralization.
Calcif Tissue Int. 2005 Sep; 77(3):167-74.CT

Abstract

The negative effect of acidosis on the skeleton has been known for almost a century. Bone mineral serves an important pathophysiologic role as a reserve of hydroxyl ions to buffer systemic protons if the kidneys and lungs are unable to maintain acid-base balance within narrow physiologic limits. Extracellular hydrogen ions are now thought to be the primary activation signal for osteoclastic bone resorption, and osteoclasts are very sensitive to small changes in pH within the pathophysiologic range. Herein, we investigated the effects of acidosis on osteoblast function by using mineralized bone nodule-forming primary osteoblast cultures. Osteoblasts harvested from neonatal rat calvariae were cultured up to 21 days in serum-containing medium, with ascorbate, beta-glycerophosphate and dexamethasone. pH was manipulated by addition of 5 to 30 mmol/L HCl and monitored by blood gas analyzer. Abundant, matrix-containing mineralized nodules formed in osteoblast cultures at pH 7.4, but acidification progressively reduced mineralization of bone nodules, with complete abolition at pH 6.9. Osteoblast proliferation and collagen synthesis, assessed by 3H-thymidine and 3H-proline incorporation, respectively, were unaffected by pH in the range 7.4 to 6.9; no effect of acidification on collagen ultrastructure and organization was evident. The apoptosis rate of osteoblasts, assessed by the enrichment of nucleosomes in cell lysates, was also unaffected by pH within this range. However, osteoblast alkaline phosphatase activity, which peaked strongly near pH 7.4, was reduced eight-fold at pH 6.9. Reducing pH to 6.9 also downregulated messenger ribonucleic acid (mRNA) for alkaline phosphatase, but upregulated mRNA for matrix Gla protein, an inhibitor of mineralization. The same pH reduction is associated with two-and four-fold increases in Ca2+ and PO4(3-) solubility for hydroxyapatite, respectively. Our results show that acidosis exerts a selective, inhibitory action on matrix mineralization that is reciprocal with the osteoclast activation response. Thus, in uncorrected acidosis, the deposition of alkaline mineral in bone by osteoblasts is reduced, and osteoclast resorptive activity is increased in order to maximize the availability of hydroxyl ions in solution to buffer protons.

Authors+Show Affiliations

Department of Anatomy and Developmental Biology, University college London, Gower Street, WC 1E 6BT London, UK.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16075362

Citation

Brandao-Burch, A, et al. "Acidosis Inhibits Bone Formation By Osteoblasts in Vitro By Preventing Mineralization." Calcified Tissue International, vol. 77, no. 3, 2005, pp. 167-74.
Brandao-Burch A, Utting JC, Orriss IR, et al. Acidosis inhibits bone formation by osteoblasts in vitro by preventing mineralization. Calcif Tissue Int. 2005;77(3):167-74.
Brandao-Burch, A., Utting, J. C., Orriss, I. R., & Arnett, T. R. (2005). Acidosis inhibits bone formation by osteoblasts in vitro by preventing mineralization. Calcified Tissue International, 77(3), 167-74.
Brandao-Burch A, et al. Acidosis Inhibits Bone Formation By Osteoblasts in Vitro By Preventing Mineralization. Calcif Tissue Int. 2005;77(3):167-74. PubMed PMID: 16075362.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acidosis inhibits bone formation by osteoblasts in vitro by preventing mineralization. AU - Brandao-Burch,A, AU - Utting,J C, AU - Orriss,I R, AU - Arnett,T R, Y1 - 2005/07/28/ PY - 2004/12/08/received PY - 2005/03/21/accepted PY - 2005/8/3/pubmed PY - 2005/11/16/medline PY - 2005/8/3/entrez SP - 167 EP - 74 JF - Calcified tissue international JO - Calcif. Tissue Int. VL - 77 IS - 3 N2 - The negative effect of acidosis on the skeleton has been known for almost a century. Bone mineral serves an important pathophysiologic role as a reserve of hydroxyl ions to buffer systemic protons if the kidneys and lungs are unable to maintain acid-base balance within narrow physiologic limits. Extracellular hydrogen ions are now thought to be the primary activation signal for osteoclastic bone resorption, and osteoclasts are very sensitive to small changes in pH within the pathophysiologic range. Herein, we investigated the effects of acidosis on osteoblast function by using mineralized bone nodule-forming primary osteoblast cultures. Osteoblasts harvested from neonatal rat calvariae were cultured up to 21 days in serum-containing medium, with ascorbate, beta-glycerophosphate and dexamethasone. pH was manipulated by addition of 5 to 30 mmol/L HCl and monitored by blood gas analyzer. Abundant, matrix-containing mineralized nodules formed in osteoblast cultures at pH 7.4, but acidification progressively reduced mineralization of bone nodules, with complete abolition at pH 6.9. Osteoblast proliferation and collagen synthesis, assessed by 3H-thymidine and 3H-proline incorporation, respectively, were unaffected by pH in the range 7.4 to 6.9; no effect of acidification on collagen ultrastructure and organization was evident. The apoptosis rate of osteoblasts, assessed by the enrichment of nucleosomes in cell lysates, was also unaffected by pH within this range. However, osteoblast alkaline phosphatase activity, which peaked strongly near pH 7.4, was reduced eight-fold at pH 6.9. Reducing pH to 6.9 also downregulated messenger ribonucleic acid (mRNA) for alkaline phosphatase, but upregulated mRNA for matrix Gla protein, an inhibitor of mineralization. The same pH reduction is associated with two-and four-fold increases in Ca2+ and PO4(3-) solubility for hydroxyapatite, respectively. Our results show that acidosis exerts a selective, inhibitory action on matrix mineralization that is reciprocal with the osteoclast activation response. Thus, in uncorrected acidosis, the deposition of alkaline mineral in bone by osteoblasts is reduced, and osteoclast resorptive activity is increased in order to maximize the availability of hydroxyl ions in solution to buffer protons. SN - 0171-967X UR - https://www.unboundmedicine.com/medline/citation/16075362/Acidosis_inhibits_bone_formation_by_osteoblasts_in_vitro_by_preventing_mineralization_ L2 - https://dx.doi.org/10.1007/s00223-004-0285-8 DB - PRIME DP - Unbound Medicine ER -