Tetraspanin 7 regulates sealing zone formation and the bone-resorbing activity of osteoclasts

• Published in: Biochemical and biophysical research communications Vol. 477; no. 4; pp. 1078 - 1084
• Main Authors: Kwon, Jun-Oh, Lee, Yong Deok, Kim, Haemin, Kim, Min Kyung, Song, Min-Kyoung, Lee, Zang Hee, Kim, Hong-Hee
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.09.2016
• Subjects: 60 APPLIED LIFE SCIENCES; ACETYLATION; Animals; Bone Resorption - metabolism; Bone Resorption - pathology; Cell Movement; Cell Survival; Cells, Cultured; DENTIN; Female; GENES; Mice; Microtubule; MICROTUBULES; MORPHOLOGY; Osteoclasts - metabolism; Osteoclasts - pathology; Osteogenesis; PHOSPHORYLATION; Podosome belt; Podosomes - metabolism; Podosomes - pathology; PROTEINS; Pyk2; Sealing zone; SKELETON; Src; Tetraspanin 7; Tetraspanins - metabolism; Sealing zone; Microtubule; Podosome belt; Src; Tetraspanin 7; Pyk2
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.07.046

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. •Tspan7 expression is up-regulated during osteoclastogenesis.•Tspan7 regulates podosome belt organization in osteoclasts.•Tspan7 is crucial for sealing zone formation and bone-resorption by osteoclasts.•Src and Pyk2 phosphorylation and microtubule acetylation mediate Tspan7 function.