Osteoclast proton transport modulation by fluid flow

Morethson, Priscilla

doi:10.1016/j.bone.2011.03.277

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“…Later, it was shown—using pH microelectrodes—that osteoclasts can acidify the contact zone with a culture dish to less than pH 3 within a few minutes [ 2 ]. It has been proposed that extracellular acidification is a key step for the dissolution of the apatite-containing mineralized matrix [ 3 , 4 ] and osteoclast intracellular pH (pH i ) regulation [ 5 – 8 ]; in addition, H + secretion creates a suitable pH, in the resorption lacuna, for enzymes to degrade the organic matrix [ 9 ]. Therefore, bone resorption depends on the expression and activity of H + -secreting proteins at the osteoclast ruffled border.…”

Section: Introductionmentioning

confidence: 99%

Extracellular fluid flow and chloride content modulate H+ transport by osteoclasts

Morethson¹

2015

BMC Cell Biol

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BackgroundBone resorption takes place within the basic multicellular units (BMU), and the surface to be resorbed is isolated from adjacent bone surfaces by a sealing zone between osteoclast membrane and bone matrix, which defines the limits of the resorption lacuna. Considering that the extracellular fluid (ECF) in both BMU and the resorption lacuna can be isolated from its surroundings, I hypothesize that flow and ion composition of the bone ECF in these sites might contribute to the regulation of osteoclast H+ secretion. To investigate this hypothesis, I evaluated the H+ secretion properties of individual osteoclasts and osteoclast-like cells (OCL-cells) and investigated whether changes in flow or chloride content of the extracellular solution modify the H+ secretion properties in vitro.ResultsThe results show that 1) osteoclasts are unable to secrete H+ and regulate intracellular pH (pHi) under continuous flow conditions and exhibit progressive intracellular acidification; 2) the cessation of flow coincides with the onset of H+ secretion and subsequent progressive intracellular alkalinization of osteoclasts and OCL-cells; 3) osteoclasts exhibit spontaneous rhythmic oscillations of pHi in non-flowing ECF, 4) pHi oscillations are not abolished by concanamycin, NPPB, or removal of extracellular Na+ or Cl−; 5) extracellular Cl− removal modifies the pattern of oscillations, by diminishing H+ secretion; 6) pHi oscillations are abolished by continuous flowing of ECF over osteoclasts and OCL-cells.ConclusionsThe data suggest, for the first time, that ECF flow and Cl− content have direct effects on osteoclast H+ secretion and could be part of a mechanism determining the onset of osteoclast H+ secretion required for bone resorption.Electronic supplementary materialThe online version of this article (doi:10.1186/s12860-015-0066-4) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Extracellular fluid flow and chloride content modulate H+ transport by osteoclasts

Morethson¹

2015

BMC Cell Biol

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Osteoclast proton transport modulation by fluid flow

Cited by 1 publication

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Extracellular fluid flow and chloride content modulate H+ transport by osteoclasts

Extracellular fluid flow and chloride content modulate H+ transport by osteoclasts

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