Acute metabolic acidosis inhibits the induction of osteoblastic egr-1 and type 1 collagen

Frick, Kevin K.; Liu, Jiang; Bushinsky, David A.

doi:10.1152/ajpcell.1997.272.5.c1450

Cited by 70 publications

(63 citation statements)

References 25 publications

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“…It is known that osteoblasts prefer moderately alkaline conditions, i.e. pH values close to 7.8, while changes in pH cause severe damage to cell viability [16][17][18]. CEL2 composition was tailored in light of this consideration, in an attempt to control pH variations.…”

Section: Resultsmentioning

confidence: 99%

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Biocompatible glass–ceramic materials for bone substitution

Brovarone

Verné

Robiglio

et al. 2007

J Mater Sci: Mater Med

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A new bioactive glass composition (CEL2) in the SiO 2 -P 2 O 5 -CaO-MgO-K 2 O-Na 2 O system was tailored to control pH variations due to ion leaching phenomena when the glass is in contact with physiological fluids. CEL2 was prepared by a traditional meltingquenching process obtaining slices that were heat-treated to obtain a glass-ceramic material (CEL2GC) that was characterized thorough SEM analysis. Pre-treatment of CEL2GC with SBF was found to enhance its biocompatibility, as assessed by in vitro tests. CEL2 powder was then used to synthesize macroporous glass-ceramic scaffolds. To this end, CEL2 powders were mixed with polyethylene particles within the 300-600 lm size-range and then pressed to obtain crack-free compacted powders (green). This was heat-treated to remove the organic phase and to sinter the inorganic phase, leaving a porous structure. The biomaterial thus obtained was characterized by X-ray diffraction, SEM equipped with EDS, density measurement, image analysis, mechanical testing and in vitro evaluation, and found to be a glass-ceramic macroporous scaffold with uniformly distributed and highly interconnected porosity. The extent and size-range of the porosity can be tailored by varying the amount and size of the polyethylene particles.

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Section: Resultsmentioning

confidence: 99%

“…It is known that osteoblasts prefer a slightly alkaline medium (7.8) [14,15], but it is also known that severe changes in pH can inhibit osteoblast activity and cause cell necrosis or apoptosis [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Biocompatible glass–ceramic materials for bone substitution

Brovarone

Verné

Robiglio

et al. 2007

J Mater Sci: Mater Med

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“…72 The reduction in osteoblast activity may also reduce the gene expression of several matrix proteins such as COL1A, OPN, and MGP, which may contribute to increased osteoarthritis development. 71,[74][75][76] Two of the pH-sensing G protein-coupled receptors, GPR68 and GPR65, have been reported to sense acidosis in bone cells.…”

Section: Role For the Ph-sensing Gpcrs In The Skeletal Systemmentioning

confidence: 99%

Emerging roles for the pH-sensing G protein-coupled receptors in response to acidotic stress

Sanderlin¹,

Justus²,

Krewson³

et al. 2015

CHC

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Protons (hydrogen ions) are the simplest form of ions universally produced by cellular metabolism including aerobic respiration and glycolysis. Export of protons out of cells by a number of acid transporters is essential to maintain a stable intracellular pH that is critical for normal cell function. Acid products in the tissue interstitium are removed by blood perfusion and excreted from the body through the respiratory and renal systems. However, the pH homeostasis in tissues is frequently disrupted in many pathophysiologic conditions such as in ischemic tissues and tumors where protons are overproduced and blood perfusion is compromised. Consequently, accumulation of protons causes acidosis in the affected tissue. Although acidosis has profound effects on cell function and disease progression, little is known about the molecular mechanisms by which cells sense and respond to acidotic stress. Recently a family of pH-sensing G protein-coupled receptors (GPCRs), including GPR4, GPR65 (TDAG8), and GPR68 (OGR1), has been identified and characterized. These GPCRs can be activated by extracellular acidic pH through the protonation of histidine residues of the receptors. Upon activation by acidosis the pH-sensing GPCRs can transduce several downstream G protein pathways such as the G s , G q/11 , and G 12/13 pathways to regulate cell behavior. Studies have revealed the biological roles of the pH-sensing GPCRs in the immune, cardiovascular, respiratory, renal, skeletal, endocrine, and nervous systems, as well as the involvement of these receptors in a variety of pathological conditions such as cancer, inflammation, pain, and cardiovascular disease. As GPCRs are important drug targets, small molecule modulators of the pH-sensing GPCRs are being developed and evaluated for potential therapeutic applications in disease treatment.

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“…Met acidosis increases osteoblastic expression of cyclooxygenase 2 (COX-2) (47) and receptor activator of NF-B ligand (RANKL) (33,35), the latter which interacts with its osteoclastic receptor RANK to stimulate bone resorption. Met acidosis also alters osteoblastic extracellular matrix by decreasing expression of type 1 collagen (7,9,19,20,34,48), osteopontin, and matrix gla protein (31,32), which limits bone formation, and increases secretion of ␤-glucuronidase by osteoclasts (7,19,48), which stimulates bone resorption.…”

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confidence: 99%