Titanium-enriched medium drives low profile of ECM remodeling as a pre-requisite to pre-osteoblast viability and proliferative phenotype

Autor(es)

da Costa Fernandes, Celio J. ^[1] ; Bezerra, Fabio J. B. ^[1] ; Souza, Bruno de Campos ^[1] ; Campos, Monica Aparecida ^[1] ; Zambuzzi, Willian Fernando ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, UNESP, Biosci Inst, Dept Chem & Biochem, Campus Botucatu, Botucatu, SP - Brazil

^[2] UNESP, IBB, Elect Microscopy, Botucatu, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY; v. 50, p. 339-346, 2018.
• Citações Web of Science: 4

Resumo

Titanium is widely used for biomedical applications, but little information is being delivered regarding the cellular/molecular mechanisms explaining their efficacy, mainly considering the effects of the Ti-released trace elements on pre-osteoblasts. We addressed this issue by investigating decisive intracellular signal transduction able to modulate cytoskeleton rearrangement, proliferative phenotype and extracellular matrix (ECM) remodeling. We considered titanium grades N and V, submitted or not to dual acid-etching (w/DAE or wo/DAE, respectively). Our results showed there is no cytotoxicity, preserving AKT involvement. Additionally, Ti-enriched medium promoted a diminution of the downstream signaling upon integrin activation (phosphorylating Rac1 and cofilin), guaranteeing a dynamic cytoskeleton rearrangement. Moreover, the low profile of ECM remodeling obtained in response to trace molecules released by Ti-based devices seems contributing to the osteoblast performance in mediating extracellular support to cell anchorage. This hypothesis was validated by the up-expression of beta 1-integrin, src and Focal adhesion kinase (fak) genes, mainly in response to titanium grade V. Proliferative phenotype showed an unbalance between cyclin-dependent kinases (CDKs) and p15(INK4b)/p21(CiP1). In conjunction, we showed for the first time that trace elements from Ti-based biomedical devices provoke important modulation of the osteoblast biology, driving cell anchoring, viability, and proliferative phenotype. Certainly, these biological outcomes compromise implant osseointegration. (AU)

• Processo FAPESP: 14/22689-3 - Sinalização parácrina mediada por microvesículas e proteínas entre células ósseas e endoteliais durante o desenvolvimento e regeneração do tecido ósseo
• Beneficiário: Willian Fernando Zambuzzi
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores