Sclerostin regulates release of bone mineral by osteocytes by induction of carbonic anhydrase 2

Masakazu Kogawa, Asiri R Wijenayaka, Renee T Ormsby, Gethin P Thomas, Paul H Anderson, Lynda F Bonewald, David M Findlay, Gerald J Atkins

    Research output: Contribution to journalArticle

    89 Citations (Scopus)

    Abstract

    The osteocyte product sclerostin is emerging as an important paracrine regulator of bone mass. It has recently been shown that osteocyte production of receptor activator of NF-κB ligand (RANKL) is important in osteoclastic bone resorption, and we reported that exogenous treatment of osteocytes with sclerostin can increase RANKL-mediated osteoclast activity. There is good evidence that osteocytes can themselves liberate mineral from bone in a process known as osteocytic osteolysis. In the current study, we investigated sclerostin-stimulated mineral dissolution by human primary osteocyte-like cells (hOCy) and mouse MLO-Y4 cells. We found that sclerostin upregulated osteocyte expression of carbonic anhydrase 2 (CA2/Car2), cathepsin K (CTSK/Ctsk), and tartrate-resistant acid phosphatase (ACP5/Acp5). Because acidification of the extracellular matrix is a critical step in the release of mineral from bone, we further examined the regulation by sclerostin of CA2. Sclerostin stimulated CA2 mRNA and protein expression in hOCy and in MLO-Y4 cells. Sclerostin induced a decrease in intracellular pH (pHi) in both cell types as well as a decrease in extracellular pH (pHo) and the release of calcium ions from mineralized substrate. These effects were reversed in the co-presence of the carbonic anhydrase inhibitor, acetozolamide.
    Original languageEnglish
    Pages (from-to)2436-2448
    Number of pages13
    JournalJournal of Bone and Mineral Research
    Volume28
    Issue number12
    DOIs
    Publication statusPublished - 2013

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