Ascorbate-induced osteoblast differentiation recruits distinct MMP-inhibitors: RECK and TIMP-2

Autor(es)

Zambuzzi, Willian F. ^[1] ; Yano, Claudia L. ^[1] ; Cavagis, Alexandre D. M. ^{[1, 2]} ; Peppelenbosch, Maikel P. ^[3] ; Granjeiro, Jose Mauro ^{[4, 5]} ; Ferreira, Carmen V. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Inst Biol, Dept Bioquim, BR-13083970 Sao Paulo - Brazil

^[2] Univ Metodista Piracicaba UNIMEP, Sao Paulo - Brazil

^[3] Univ Groningen Groningen, Univ Med Ctr Groningen, Dept Cell Biol, Kinome Profiling Unit, Groningen - Netherlands

^[4] Univ Fed Fluminense, Inst Biol, Dept Biol Celular & Mol, Rio De Janeiro - Brazil

^[5] Univ Sao Paulo, Nucl Terapia Celular & Mol Nucell, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Cellular Biochemistry; v. 322, n. 1-2, p. 143-150, FEB 2009.
• Citações Web of Science: 29

Resumo

The bone formation executed by osteoblasts represents an interesting research field both for basic and applied investigations. The goal of this work was to evaluate the molecular mechanisms involved during osteoblast differentiation in vitro. Accordingly, we demonstrated that, during the osteoblastic differentiation, TIMP-2 and RECK presented differential expressions, where RECK expression was downregulated from the 14th day in contrast with an increase in TIMP-2. Concomitantly, our results showed a temporal regulation of two major signaling cascades during osteoblast differentiation: proliferation cascades in which RECK, PI3 K, and GSK-3 beta play a pivotal role and latter, differentiation cascades with participation of Ras, Rho, Rac-1, PKC alpha/beta, and TIMP-2. Furthermore, we observed that phosphorylation level of paxillin was downregulated while FAK(125) remained unchangeable, but active during extracellular matrix (ECM) remodeling. Concluding, our results provide evidences that RECK and TIMP-2 are involved in the control of ECM remodeling in distinct phases of osteoblast differentiation by modulating MMP activities and a multitude of signaling proteins governs these events. (AU)

• Processo FAPESP: 04/14906-2 - Mecanismos moleculares induzidos pela matriz de colágeno durante a osteogênese in vitro
• Beneficiário: Willian Fernando Zambuzzi
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto