title: Tetraspanin 7 regulates sealing zone formation and the bone-resorbing activity of osteoclasts.
abstract: Tetraspanin family proteins regulate morphology, motility, fusion, and signaling in various cell types. We investigated the role of the tetraspanin 7 (Tspan7) isoform in the differentiation and function of osteoclasts. Tspan7 was up-regulated during osteoclastogenesis. When Tspan7 expression was reduced in primary precursor cells by siRNA-mediated gene knock-down, the generation of multinuclear osteoclasts was not affected. However, a striking cytoskeletal abnormality was observed: the formation of the podosome belt structure was inhibited and the microtubular network were disrupted by Tspan7 knock-down. Decreases in acetylated microtubules and levels of phosphorylated Src and Pyk2 in Tspan7 knock-down cells supported the involvement of Tspan7 in cytoskeletal rearrangement signaling in osteoclasts. This cytoskeletal defect interfered with sealing zone formation and subsequently the bone-resorbing activity of mature osteoclasts on dentin surfaces. Our results suggest that Tspan7 plays an important role in cytoskeletal organization required for the bone-resorbing function of osteoclasts by regulating signaling to Src, Pyk2, and microtubules.
authors.affiliation: Department of Cell and Developmental Biology, BK21 Program and DRI, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
authors.forename: Jun-Oh
authors.initials: JO
authors.lastname: Kwon
authors.affiliation: Department of Cell and Developmental Biology, BK21 Program and DRI, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
authors.forename: Yong Deok
authors.initials: YD
authors.lastname: Lee
authors.affiliation: Department of Cell and Developmental Biology, BK21 Program and DRI, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
authors.forename: Haemin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Cell and Developmental Biology, BK21 Program and DRI, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Cell and Developmental Biology, BK21 Program and DRI, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
authors.forename: Min-Kyoung
authors.initials: MK
authors.lastname: Song
authors.affiliation: Department of Cell and Developmental Biology, BK21 Program and DRI, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
authors.forename: Zang Hee
authors.initials: ZH
authors.lastname: Lee
authors.affiliation: Department of Cell and Developmental Biology, BK21 Program and DRI, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea. Electronic address: hhbkim@snu.ac.kr.
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D051379:Mice; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology*; D010012:Osteogenesis; D000069261:Podosomes / Q000378:metabolism* / Q000473:pathology; D059470:Tetraspanins / Q000378:metabolism*
chemical_list: D059470:Tetraspanins
keywords: Microtubule; Podosome belt; Pyk2; Sealing zone; Src; Tetraspanin 7