Stimulated osteoclastic and suppressed osteoblastic activity in metabolic but not respiratory acidosis

1995 ◽  
Vol 268 (1) ◽  
pp. C80-C88 ◽  
Author(s):  
D. A. Bushinsky
Keyword(s):  
Alkaline Phosphatase ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Collagen Synthesis ◽  
Cell Function ◽  
Respiratory Acidosis ◽  
Bone Cell ◽  
Calcium Efflux ◽  
Osteoblastic Activity ◽  
Glucuronidase Activity

When bone is cultured in acidic medium produced by a reduced bicarbonate concentration ([HCO(3-)]), a model of metabolic acidosis, there is greater net calcium efflux than when the same decrement in pH is produced by an increased partial pressure of carbon dioxide (PCO2), a model of respiratory acidosis. To determine the effects of metabolic and respiratory acidosis on bone cell function we cultured neonatal mouse calvariae for 48 h under control conditions (pH approximately 7.40, PCO2 approximately 41 mmHg, [HCO(3-)] approximately 25 meq/l) or under isohydric acidic conditions simulating metabolic (pH approximately 7.09, [HCO(3-)] approximately 12) or respiratory (pH approximately 7.10, PCO2 approximately 86) acidosis and measured osteoblastic collagen synthesis and alkaline phosphatase activity and osteoclastic beta-glucuronidase activity. Collagen synthesis was inhibited by metabolic (23.2 +/- 1.3 vs. 30.3 +/- 1.0% in control) but was not altered by respiratory (32.3 +/- 0.6) acidosis. Alkaline phosphatase activity was inhibited by metabolic (402 +/- 16 vs. 471 +/- 15 nmol P.min-1.mg protein-1 in control) but not altered by respiratory (437 +/- 25) acidosis. beta-Glucuronidase activity was stimulated by metabolic (1.02 +/- 0.06 vs. 0.78 +/- 0.05 micrograms phenolphthalein released.bone-1.h-1 in control) but not altered by respiratory (0.73 +/- 0.06) acidosis. Net calcium efflux in control was increased by metabolic (783 +/- 57 vs. 20 +/- 57 nmol.bone-1.48 h-1 in control) and by respiratory (213 +/- 45) acidosis; however, calcium efflux with metabolic was greater than with respiratory acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis inhibits osteoblastic and stimulates osteoclastic activity in vitro

1992 ◽  
Vol 262 (3) ◽  
pp. F442-F448 ◽  
Author(s):  
N. S. Krieger ◽  
N. E. Sessler ◽  
D. A. Bushinsky
Keyword(s):  
Alkaline Phosphatase ◽  
Metabolic Acidosis ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Collagen Synthesis ◽  
Calcium Flux ◽  
Osteoclastic Activity ◽  
Glucuronidase Activity

Metabolic acidosis induces net calcium flux (JCa) from cultured neonatal mouse calvariae through physicochemical and cell-mediated mechanisms. To determine the role of osteoblasts in acid-induced JCa, collagen synthesis and alkaline phosphatase activity were assessed in calvariae incubated in reduced pH and bicarbonate medium, a model of metabolic acidosis (Met), and compared with controls (Ctl). Collagen synthesis fell from 30.5 +/- 1.1 in Ctl to 25.1 +/- 0.4% with Met, and alkaline phosphatase decreased from 403 +/- 25 in Ctl to 298 +/- 21 nmol Pi.min-1.mg protein-1 with Met. During acidosis JCa was correlated inversely with percent collagen synthesis (r = -0.743, n = 11, P = 0.009) and with alkaline phosphatase activity (r = -0.453, n = 22, P = 0.034). To determine the role of osteoclasts in acid-induced JCa, osteoclastic beta-glucuronidase activity was determined in Ctl and Met in the absence or presence of the osteoclastic inhibitor calcitonin (CT, 3 x 10(-9) M). Met increased beta-glucuronidase (5.9 +/- 0.2) compared with Ctl (4.6 +/- 0.3 micrograms phenolphthalein released.bone-1.h-1), whereas CT inhibited beta-glucuronidase in both Ctl and Met (3.1 +/- 0.2 and 3.5 +/- 0.3, respectively). During acidosis JCa was correlated directly with beta-glucuronidase activity (r = 0.683, n = 42, P less than 0.001). Thus the cell-mediated component of JCa during acidosis in vitro appears to result from a combination of inhibited osteoblastic and stimulated osteoclastic activity.

Additive effects of acidosis and parathyroid hormone on mouse osteoblastic and osteoclastic function

1995 ◽  
Vol 269 (6) ◽  
pp. C1364-C1370 ◽  
Author(s):  
D. A. Bushinsky ◽  
E. L. Nilsson
Keyword(s):  
Parathyroid Hormone ◽  
Collagen Synthesis ◽  
Cell Function ◽  
Inverse Correlation ◽  
Bone Cell ◽  
Additive Effects ◽  
Calcium Efflux ◽  
Glucuronidase Activity ◽  
Stage Renal Disease ◽  
End Stage

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.

scholarly journals Simultaneous autoradiographic and histochemical analysis of bone formed in vitro.

1986 ◽  
Vol 34 (6) ◽  
pp. 769-773 ◽  
Author(s):  
H C Tenenbaum ◽  
C A McCulloch ◽  
K Palangio
Keyword(s):  
Alkaline Phosphatase ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Time Course ◽  
Bone Cell ◽  
Histochemical Demonstration ◽  
Thymidine Uptake ◽  
Kinetics In Vivo

The simultaneous histochemical demonstration of alkaline phosphatase activity and autoradiographic demonstration of [3H]-thymidine uptake is valuable for study of bone cell kinetics in vivo or in vitro. By use of this technique, it has been possible to detect changes induced by a single dose of dexamethasone (10(-7) M) in the time course of alkaline phosphatase activity, the number of alkaline phosphatase-positive cells, and [3H]-thymidine labeling in bone formed in vitro.

scholarly journals Effect of Magnolol on the Function of Osteoblastic MC3T3-E1 Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Eun Jung Kwak ◽  
Young Soon Lee ◽  
Eun Mi Choi
Keyword(s):  
Alkaline Phosphatase ◽  
Cell Growth ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Collagen Synthesis ◽  
Osteoclast Differentiation ◽  
Osteoblast Function ◽  
Receptor Activator ◽  
Inducing Factors ◽  
Magnolia Officinalis

Objectives.In the present study, the ability of magnolol, a hydroxylated biphenyl compound isolated fromMagnolia officinalis, to stimulate osteoblast function and inhibit the release of bone-resorbing mediators was investigated in osteoblastic MC3T3-E1 cells.Methods.Osteoblast function was measured by cell growth, alkaline phosphatase activity, collagen synthesis, and mineralization. Glutathione content was also measured in the cells. Bone-resorbing cytokines, receptor activator of nuclear factor-κB ligand (RANKL), TNF-α, and IL-6 were measured with an enzyme immunoassay system.Results.Magnolol caused a significant elevation of cell growth, alkaline phosphatase activity, collagen synthesis, mineralization, and glutathione content in the cells (P<0.05). Skeletal turnover is orchestrated by a complex network of regulatory factors. Among cytokines, RANKL, TNF-α, and IL-6 were found to be key osteoclastogenetic molecules produced by osteoblasts. Magnolol significantly (P<0.05) decreased the production of osteoclast differentiation inducing factors such as RANKL, TNF-α, and IL-6 in the presence of antimycin A, which inhibits mitochondrial electron transport and has been used as an ROS generator.Conclusion.Magnolol might be a candidate as an agent for the prevention of bone disorders such as osteoporosis.

Influence of osteoclasts and osteoclast-like cells on osteoblast alkaline phosphatase activity and collagen synthesis

2009 ◽  
Vol 9 (8) ◽  
pp. 1167-1178 ◽  
Author(s):  
Rachelle J. Sells Galvin ◽  
James W. Cullison ◽  
Louis V. Avioli ◽  
Philip A. Osdoby
Keyword(s):  
Alkaline Phosphatase ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Collagen Synthesis

In vitro metabolic and respiratory acidosis selectively inhibit osteoblastic matrix gene expression

1999 ◽  
Vol 277 (5) ◽  
pp. F750-F755 ◽  
Author(s):  
Kevin K. Frick ◽  
David A. Bushinsky
Keyword(s):  
Metabolic Acidosis ◽  
Collagen Synthesis ◽  
Bone Cells ◽  
Respiratory Acidosis ◽  
Bone Cell ◽  
Matrix Gla Protein ◽  
Calcium Excretion ◽  
Calcium Efflux ◽  
Matrix Gene ◽  
Significant Difference

Clinically, a decrease in blood pH may be due to either a reduction in bicarbonate concentration ([H[Formula: see text]], metabolic acidosis) or an increase in[Formula: see text] (respiratory acidosis). In mammals, metabolic acidosis induces a far greater increase in urine calcium excretion than respiratory acidosis. In cultured bone, metabolic acidosis induces a marked increase in calcium efflux and a decrease in osteoblastic collagen synthesis, whereas isohydric respiratory acidosis has little effect on either parameter. We have shown that metabolic acidosis prevents the normal developmental increase in the expression of RNA for matrix Gla protein and osteopontin in chronic cultures of primary murine calvarial bone cells (predominantly osteoblasts) but does not alter expression of osteonectin. To compare the effects of isohydric metabolic and respiratory acidosis on expression of these genes, bone cell cultures were incubated in medium at pH ∼7.2 to model metabolic ([H[Formula: see text]], ∼13 mM) or respiratory ([Formula: see text], ∼80 mmHg) acidosis or at pH ∼7.4 as a control. Cells were sampled at weeks 4, 5, and 6 to assess specific RNA content. At all time periods studied, both metabolic and respiratory acidosis inhibited the expression of RNA for matrix Gla protein and osteopontin to a similar extent, whereas there was no change in osteonectin expression. In contrast to the significant difference in the effects of metabolic and respiratory acidosis on bone calcium efflux and osteoblastic collagen synthesis, these two forms of acidosis have a similar effect on osteoblastic RNA expression of both matrix Gla protein and osteopontin. Thus, although several aspects of bone cell function are dependent on the type of acidosis, expression of these two matrix genes appears to be regulated by extracellular pH, independently of the type of acidosis.

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