Abstract
During bone resorption, the osteoclast must sustain an extraordinarily low pH environment, withstand immense ionic pressures, and coordinate nutrient and waste exchange across its membrane to sustain its unique structural and functional polarity. To achieve this, osteoclasts are equipped with an elaborate set of membrane transport proteins (pumps, transporters and channels) that serve as molecular ‘gatekeepers’ to regulate the bilateral exchange of ions, amino acids, metabolites and macromolecules across the ruffled border and basolateral domains. Whereas the importance of the vacuolar-ATPase proton pump and chloride voltage-gated channel 7 in osteoclasts has long been established, comparatively little is known about the contributions of other membrane transport proteins, including those categorized as secondary active transporters. In this Special Issue review, we provide a contemporary update on the ‘ins and outs’ of membrane transport proteins implicated in osteoclast differentiation, function and bone homeostasis and discuss their therapeutic potential for the treatment of metabolic bone diseases.
Highlights
Osteoclasts (OCs) are large bone-digesting cells that play a central role in the regulation of skeletal bone mass and bone pathologies such as osteoporosis
Whereas the importance of the vacuolar-ATPase proton pump and chloride voltage-gated channel 7 in osteoclasts has long been established, comparatively little is known about the contributions of other membrane transport proteins, including those categorized as secondary active transporters. In this Special Issue review, we provide a contemporary update on the ‘ins and outs’ of membrane transport proteins implicated in osteoclast differentiation, function and bone homeostasis and discuss their therapeutic potential for the treatment of metabolic bone diseases
TRPV5 is primarily expressed in the kidney, intestines and OCs where it plays a central role in the systemic regulation of Ca2+ homeostasis by facilitating: (i) Ca2+ reabsorption in the kidneys, (ii) absorption of dietary Ca2+ by intestinal cells, and (iii) the release of the ion by active OCs
Summary
Osteoclasts (OCs) are large bone-digesting (resorbing) cells that play a central role in the regulation of skeletal bone mass and bone pathologies such as osteoporosis. Localization and function of these membrane transport proteins in OCs and bone as well as discuss their therapeutic utility as molecular targets for the treatment of metabolic bone diseases such as osteoporosis.
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