본문 바로가기
KERD
논문KCI 등재

Selective regulation of osteoclast adhesion and spreading by PLCγ/PKCα-PKCδ/RhoA-Rac1 signaling

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류화학

초록

Bone resorption by multinucleated osteoclasts is a multistep process involving adhesion to the bone matrix, migration to resorption sites, and formation of sealing zones and ruffled borders. Macrophage colony-stimulating factor (M-CSF) and osteopontin (OPN) have been shown to be involved in the bone resorption process by respective activation of integrin αvβ3 via "inside-out" and "outside-in" signaling. In this study, we investigated the link between signal modulators known to M-CSF- and OPN-induced osteoclast adhesion and spreading. M-CSF- and OPN-induced osteoclast adhesion was achieved via activation of stepwise signals, including integrin αvβ3, PLCγ, PKCδ, and Rac1. Osteoclast spreading induced by M-CSF and OPN was shown to be controlled via sequential activation, consistent with the osteoclast adhesion processes. In contrast to osteoclast adhesion, osteoclast spreading induced by M-CSF and OPN was blocked via activation of PLCγ/PKCα/RhoA signaling. The combined results indicate that osteoclast adhesion and spreading are selectively regulated via PLCγ/PKCα-PKCδ/RhoA-Rac1 signaling.

Abstract

Bone resorption by multinucleated osteoclasts is a multistep process involving adhesion to the bone matrix, migration to resorption sites, and formation of sealing zones and ruffled borders. Macrophage colony-stimulating factor (M-CSF) and osteopontin (OPN) have been shown to be involved in the bone resorption process by respective activation of integrin αvβ3 via "inside-out" and "outside-in" signaling. In this study, we investigated the link between signal modulators known to M-CSF- and OPN-induced osteoclast adhesion and spreading. M-CSF- and OPN-induced osteoclast adhesion was achieved via activation of stepwise signals, including integrin αvβ3, PLCγ, PKCδ, and Rac1. Osteoclast spreading induced by M-CSF and OPN was shown to be controlled via sequential activation, consistent with the osteoclast adhesion processes. In contrast to osteoclast adhesion, osteoclast spreading induced by M-CSF and OPN was blocked via activation of PLCγ/PKCα/RhoA signaling. The combined results indicate that osteoclast adhesion and spreading are selectively regulated via PLCγ/PKCα-PKCδ/RhoA-Rac1 signaling.

참고문헌 (29)

  1. Boyle WJ, "Osteoclast differentiation and activation", Nature, 423, pp.337~342 (2003)[DOI]
  2. Touaitahuata H, "Modulation of osteoclast differentiation and bone resorption by Rho GTPases", Small GTPases, 5, pp.e28119~ (2014)[DOI]
  3. Georgess D, "Podosome organization drives osteoclast-mediated bone resorption", Cell Adh Migr, 8, pp.191~204 (2014)
  4. Raggatt LJ, "Cellular and molecular mechanisms of bone remodeling", J Biol Chem, 285, pp.25103~25108 (2010)[DOI]
  5. Faccio R, "Dynamic changes in the osteoclast cytoskeleton in response to growth factors and cell attachment are controlled by beta3 integrin", J Cell Biol, 162, pp.499~509 (2003)[DOI]
  6. Ross FP, "Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin alpha v beta 3 potentiate bone resorption", J Biol Chem, 268, pp.9901~9907 (1993)
  7. Ross FP, "alphavbeta3 and macrophage colony-stimulating factor: partners in osteoclast biology", Immunol Rev, 208, pp.88~105 (2005)[DOI]
  8. Pfaff M, "Podosomes in osteoclast-like cells: structural analysis and cooperative roles of paxillin, proline-rich tyrosine kinase 2 (Pyk2) and integrin alphaVbeta3", J Cell Sci, 114, pp.2775~2786 (2001)
  9. Lakkakorpi PT, "Phosphatidylinositol 3-kinase association with the osteoclast cytoskeleton, and its involvement in osteoclast attachment and spreading", Exp Cell Res, 237, pp.296~306 (1997)[DOI]
  10. Nakamura I, "Convergence of alpha(v)beta(3) integrin- and macrophage colony stimulating factor-mediated signals on phospholipase Cgamma in prefusion osteoclasts", J Cell Biol, 152, pp.361~373 (2001)[DOI]
  11. Zhang D, "The small GTP-binding protein, rho p21, is involved in bone resorption by regulating cytoskeletal organization in osteoclasts", J Cell Sci, 108, pp.2285~2292 (1995)
  12. Rucci N, "A novel protein kinase C alphadependent signal to ERK1", 2 activated by alphaVbeta3 integrin in osteoclasts and in Chinese hamster ovary (CHO) cells, 2005, pp.118, 3263~3275
  13. Horne WC, "The role(s) of Src kinase and Cbl proteins in the regulation of osteoclast differentiation and function", Immunol Rev, 208, pp.106~125 (2005)[DOI]
  14. Tanabe N, "Osteopontin signals through calcium and nuclear factor of activated T cells (NFAT) in osteoclasts: a novel RGD-dependent pathway promoting cell survival", J Biol Chem, 286, pp.39871~39881 (2011)[DOI]
  15. Epple H, "Phospholipase Cgamma2 modulates integrin signaling in the osteoclast by affecting the localization and activation of Src kinase", Mol Cell Biol, 28, pp.3610~3622 (2008)[DOI]
  16. Berridge MJ, "Inositol trisphosphate and calcium signalling", Nature, 361, pp.315~325 (1993)[DOI]
  17. Tatin F, "A signalling cascade involving PKC, Src and Cdc42 regulates podosome assembly in cultured endothelial cells in response to phorbol ester", J Cell Sci, 119, pp.769~781 (2006)[DOI]
  18. Jung SY, "Protein kinase Calpha", beta inhibitor Go6976 promotes PC12 cell adhesion and spreading through membrane recruitment and activation of protein kinase Cdelta, 2013, pp.319, 153~160
  19. Ory S, "Rho and Rac exert antagonistic functions on spreading of macrophage-derived multinucleated cells and are not required for actin fiber formation", J Cell Sci, 113, pp.1177~1188 (2000)
  20. Teti A, "Colony stimulating factor-1-induced osteoclast spreading depends on substrate and requires the vitronectin receptor and the c-src proto-oncogene", J Bone Miner Res, 13, pp.50~58 (1998)[DOI]
  21. Miranti CK, "Protein kinase C regulates integrin-induced activation of the extracellular regulated kinase pathway upstream of Shc", J Biol Chem, 274, pp.10571~10581 (1999)[DOI]
  22. Kim JM, "Distinctive and selective route of PI3K", PKCalpha-PKCdelta, Mol Cell Endocrinol, pp.2016, 437[DOI]
  23. Allen WE, "Rho, Rac and Cdc42 regulate actin organization and cell adhesion in macrophages", J Cell Sci, 110, pp.707~720 (1997)
  24. Wells CM, "Rac1-deficient macrophages exhibit defects in cell spreading and membrane ruffling but not migration", J Cell Sci, 117, pp.1259~1268 (2004)[DOI]
  25. Kandabashi T, "Evidence for protein kinase C-mediated activation of Rho-kinase in a porcine model of coronary artery spasm", Arterioscler Thromb Vasc Biol, 23, pp.2209~2214 (2003)[DOI]
  26. Hotokezaka H, "U0126 and PD98059, specific inhibitors of MEK, accelerate differentiation of RAW264.7 cells into osteoclast-like cells", J Biol Chem, 277, pp.47366~47372 (2002)[DOI]
  27. Lee K, "Selective Regulation of MAPK Signaling Mediates RANKL-dependent Osteoclast Differentiation", Int J Biol Sci, 12, pp.235~245 (2016)[DOI]
  28. Nakamura I, "Role of alpha(v)beta(3) integrin in osteoclast migration and formation of the sealing zone", J Cell Sci, 112, pp.3985~3993 (1999)
  29. Jung SY, "A biologically active sequence of the laminin alpha2 large globular 1 domain promotes cell adhesion through syndecan-1 by inducing phosphorylation and membrane localization of protein kinase Cdelta", J Biol Chem, 284, pp.31764~31775 (2009)[DOI]

관련 논문AI추천

Vav1 inhibits RANKL-induced osteoclast differentiation and bone resorption강인순, 김영준, 김채균, 이장희, 장진선, 차영남, Mary C Dinauer생화학분자생물학회 · BMB Reports2019 · 제52권 제11호Phospholipase C β4 promotes RANKL-dependent osteoclastogenesis by interacting with MKK3 and p38 MAPKChe Xiangguo, Choi Je-Yong, Choi Poo-Reum, Cui Ying, Hur Keun, Jin Xian, Kim Hyun-Ju, Lee Dong-Kyo, Lee Sihoon생화학분자생물학회 · Experimental and Molecular Medicine2025 · 제57권 Phospholipase D2 controls bone homeostasis by modulating M-CSF-dependent osteoclastic cell migration and microtubule stability최제용, Che Xiangguo, Jin Xian, Kim Hyun-Ju, Lee Dong-Kyo, Ryu Sung Ho생화학분자생물학회 · Experimental and Molecular Medicine2022 · 제54권 Protocadherin-7 contributes to maintenance of bone homeostasis through regulation of osteoclast multinucleationHyunsoo Kim, Jun Ueda, Masahito Ikawa, Matthew C. Walsh, Noriko Takegahara, Yongwon Choi, Yoshitaka Fujihara생화학분자생물학회 · BMB Reports2020 · 제53권 제9호Actin-binding LIM protein 1 regulates receptor activator of NF-κB ligand-mediated osteoclast differentiation and motility구동륜, 김현수, 박근하, 이승훈, 이영래, 진수현, 최용원생화학분자생물학회 · BMB Reports2018 · 제51권 제7호Unraveling the intricacies of osteoclast differentiation and maturation: insight into novel therapeutic strategies for bone-destructive diseasesChoi Yongwon, Kim Hyunsoo, Takegahara Noriko생화학분자생물학회 · Experimental and Molecular Medicine2024 · 제56권

이 간행물의 다른 논문 (9건)