V-ATPase V0 subunit d2-deficient mice exhibit impaired osteoclast fusion and increased bone formation

Seoung Hoon Lee, Jaerang Rho, Daewon Jeong, Jai Yoon Sul, Taesoo Kim, Nacksung Kim, Ju Seob Kang, Takeshi Miyamoto, Toshio Suda, Sun Kyeong Lee, Robert J. Pignolo, Boguslawa Koczon-Jaremko, Joseph Lorenzo, Yongwon Choi

研究成果: Article査読

412 被引用数 (Scopus)

抄録

Matrix-producing osteoblasts and bone-resorbing osteoclasts maintain bone homeostasis. Osteoclasts are multinucleated, giant cells of hematopoietic origin formed by the fusion of mononuclear pre-osteoclasts derived from myeloid cells. Fusion-mediated giant cell formation is critical for osteoclast maturation; without it, bone resorption is inefficient. To understand how osteoclasts differ from other myeloid lineage cells, we previously compared global mRNA expression patterns in these cells and identified genes of unknown function predominantly expressed in osteoclasts, one of which is the d2 isoform of vacuolar (H +) ATPase (v-ATPase) V0 domain (Atp6v0d2). Here we show that inactivation of Atp6v0d2 in mice results in markedly increased bone mass due to defective osteoclasts and enhanced bone formation. Atp6v0d2 deficiency did not affect differentiation or the v-ATPase activity of osteoclasts. Rather, Atp6v0d2 was required for efficient pre-osteoclast fusion. Increased bone formation was probably due to osteoblast-extrinsic factors, as Atp6v02 was not expressed in osteoblasts and their differentiation ex vivo was not altered in the absence of Atp6v02. Our results identify Atp6v0d2 as a regulator of osteoclast fusion and bone formation, and provide genetic data showing that it is possible to simultaneously inhibit osteoclast maturation and stimulate bone formation by therapeutically targeting the function of a single gene.

本文言語English
ページ(範囲)1403-1409
ページ数7
ジャーナルNature medicine
12
12
DOI
出版ステータスPublished - 2006 12

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学(全般)

フィンガープリント

「V-ATPase V<sub>0</sub> subunit d2-deficient mice exhibit impaired osteoclast fusion and increased bone formation」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル