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

BMC Cell Biology

Priscilla Morethson¹ 

[1] Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil

关键词: Bis-carboxyethyl-carboxyfluorescein-AM (BCECF-AM);    Fluorescence microscopy;    Bone extracellular fluid;    Bone resorption;    Proton secretion;    ClC-7;    Intracellular pH regulation;    Osteoclast;   

Others  :  1222816
DOI  :  10.1186/s12860-015-0066-4

 received in 2015-02-26, accepted in 2015-07-28,  发布年份 2015

【 摘 要 】

Background

Bone 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.

Results

The results show that 1) osteoclasts are unable to secrete H ⁺and regulate intracellular pH (pH _i ) 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 pH _iin non-flowing ECF, 4) pH _ioscillations 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) pH _ioscillations are abolished by continuous flowing of ECF over osteoclasts and OCL-cells.

Conclusions

The 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.

【 授权许可】

   
2015 Morethson.

【 图 表 】

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