Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:A7KAX9 (grit)
 1,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When osteoblasts are cultured on surfaces of increasing microroughness, they exhibit decreases in proliferation, increases in differentiation and local factor production, and enhanced response to 1alpha,25(OH)(2)D(3). The cells interact with surfaces through integrins, which signal by the same pathways used by 1alpha,25(OH)(2)D(3), including protein kinase C via phospholipase C and protein kinase A via phospholipase A(2). This provides opportunities for crosstalk that may contribute to the synergistic effects of surface roughness and the vitamin D metabolite. Because these pathways converge at mitogen-activated protein kinase (MAPK), we tested the hypothesis that the extracellular signal-regulated kinase (ERK1/2) subclass of MAPKs mediates the effects of surface roughness and 1alpha,25(OH)(2)D(3). MG63 osteoblast-like osteosarcoma cells were cultured on commercially pure Ti disks with various surface roughnesses: pretreatment (PT; 0.6 microm average roughness [Ra]), coarse grit-blasted and acid-etched (SLA; 4 microm RA), and titanium plasma-sprayed (TPS; 5.2-microm R(a)). At confluence, cells were treated for 24 h with control media or media containing 10(-7) M 1alpha,25(OH)(2)D(3). One-half of the cultures received 1 microm or 10 microm PD98059, a specific inhibitor of the ERK family of MAPKs. PD98059 alone did not affect proliferation, osteocalcin production, or production of transforming growth factor-beta1 or nitric oxide, regardless of the surface roughness. Alkaline phosphatase was reduced by the inhibition of the ERK family kinases on all surfaces to a comparable extent. However, when PD98059 was added to the cultures with 1alpha,25(OH)(2)D(3), the effects of the seco-steroid were blocked, including the synergistic increases seen in MG63 cells cultured on SLA or TPS. These results indicate that ERK1/2 MAPK is required for the maintenance of alkaline phosphatase at control levels and that the effects of 1alpha,25(OH)(2)D(3) are mediated by ERK1/2. However, the effects of surface roughness are not due to the ERK family of MAPKs. This suggests that alternative pathways may be used, including those mediated by other MAPK subclasses.
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PMID:Osteoblast response to titanium surface roughness and 1alpha,25-(OH)(2)D(3) is mediated through the mitogen-activated protein kinase (MAPK) pathway. 1137 60

Implant surface topography can modulate macrophage behavior during wound healing by the production of proinflammatory cytokines. This study investigated the activation of FAK, Src, and ERK1/2 signaling intermediates of the proinflammatory ERK1/2 pathway in RAW 264.7 macrophages in response to polished (P), coarse-grit-blasted (B), acid etched (E), and grit-blasted and etched (SLA) surface topographies. In addition, the effects of these topographies on cell spreading, vinculin organization, and viability were determined. Macrophages on the SLA surface changed from predominantly well-spread cells to ones with a more spherical morphology over time. In contrast, macrophages on the P surface changed from being predominantly spherical cells to well spread. The morphological changes were associated with changes in the distribution of vinculin. The overall patterns of the pFAK, pSrc, pERK1/2 levels as well as pERK1/2 nuclear translocation associated with cell shape with greater activation being seen with a more spread morphology. These results suggest that surface topography differentially activates signaling pathways that affect cell function and raise the possibility that topographies can be designed to optimize desired cell responses.
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PMID:The effect of surface topography on cell shape and early ERK1/2 signaling in macrophages; linkage with FAK and Src. 2342 18