@article{TEXTUAL,
      recid = {11714},
      author = {Tourkova, Irina L. and Larrouture, Quitterie C. and Liu,  Silvia and Luo, Jianhua and Shipman, Katherine E. and  Onwuka, Kelechi M. and Weisz, Ora A. and Riazanski,  Vladimir and Nelson, Deborah J. and MacDonald, Matthew L.  and Schlesinger, Paul H. and Blair, Harry C.},
      title = {Chloride/proton antiporters ClC3 and ClC5 support bone  formation in mice},
      journal = {Bone Reports},
      address = {2024-04-16},
      number = {TEXTUAL},
      abstract = {Acid transport is required for bone synthesis by  osteoblasts. The osteoblast basolateral surface extrudes  acid by Na&lt;sup&gt;+&lt;/sup&gt;/H&lt;sup&gt;+&lt;/sup&gt; exchange, but apical  proton uptake is undefined. We found high expression of the  Cl&lt;sup&gt;−&lt;/sup&gt;/H&lt;sup&gt;+&lt;/sup&gt; exchanger ClC3 at the bone  apical surface. In mammals ClC3 functions in intracellular  vesicular chloride transport, but when we found  Cl&lt;sup&gt;−&lt;/sup&gt; dependency of H&lt;sup&gt;+&lt;/sup&gt; transport in  osteoblast membranes, we queried whether ClC3  Cl&lt;sup&gt;−&lt;/sup&gt;/H&lt;sup&gt;+&lt;/sup&gt; exchange functions in bone  formation. We used ClC3 knockout animals, and  closely-related ClC5 knockout animals: &lt;em&gt;In vitro&lt;/em&gt;  studies suggested that both ClC3 and ClC5 might support  bone formation. Genotypes were confirmed by total exon  sequences. Expression of ClC3, and to a lesser extent of  ClC5, at osteoblast apical membranes was demonstrated by  fluorescent antibody labeling and electron microscopy with  nanometer gold labeling. Animals with ClC3 or ClC5  knockouts were viable. In ClC3 or ClC5 knockouts, bone  formation decreased ~40&amp;nbsp;% by calcein and xylenol  orange labeling &lt;em&gt;in vivo&lt;/em&gt;. In very sensitive  micro-computed tomography, ClC5 knockout reduced bone  relative to wild type, consistent with effects of ClC3  knockout, but varied with specific histological parameters.  Regrettably, ClC5-ClC3 double knockouts are not viable,  suggesting that ClC3 or ClC5 activity are essential to  life. We conclude that ClC3 has a direct role in bone  formation with overlapping but probably slightly smaller  effects of ClC5. The mechanism in mineral formation might  include ClC H&lt;sup&gt;+&lt;/sup&gt; uptake, in contrast to ClC3 and  ClC5 function in cell vesicles or other organs.},
      url = {http://knowledge.uchicago.edu/record/11714},
}