Cytoskeletal reorganisation, 1alpha,25-dihydroxy vitamin D3 and human MG63 osteoblast maturation.
Bone tissue is especially receptive to physical stimulation and agents with the capacity to mimic the signalling incurred via mechanical loading on osteoblasts may find an application in a bone regenerative setting. Recently this laboratory revealed that the major serum lipid, lysophosphatidic acid (LPA), co-operated with 1alpha,25-dihydroxy vitamin D3 (D3) in stimulating human osteoblast maturation. Actin stress fiber accrual in LPA treated osteoblasts would have generated peripheral tension which in turn may have heightened the maturation response of these cells to D3. To test this hypothesis we examined if other agents known to trigger stress fiber accumulation co-operated with D3 in stimulating human osteoblast maturation. Colchicine, nocodazole and LPA all co-operated with D3 to promote MG63 maturation in a MEK dependent manner. In contrast, calpeptin, a direct activator of Rho kinase and stress fiber accumulation did not act with D3 to secure MG63 differentiation. Herein we describe how the signalling elicited via microtubule disruption cooperates with D3 in the development of mature osteoblasts.
Mansell
Jason Peter
JP
Department of Oral & Dental Science, University of Bristol Dental School, Lower Maudlin St., Bristol, BS1 2LY, UK. j.p.mansell@bris.ac.uk
Farrar
David
D
Jones
Scott
S
Nowghani
Maryam
M
D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D003078:Colchicine / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D015739:Nocodazole / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D015675:Osteocalcin / Q000378:metabolism; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D022502:Stress Fibers / Q000187:drug effects* / Q000648:ultrastructure; D018808:Transcription Factor AP-1 / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology; D048490:raf Kinases / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D004151:Dipeptides; D008246:Lysophospholipids; D009025:Morpholines; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; C524632:TAE226; D018808:Transcription Factor AP-1; D050257:Tubulin Modulators; D015675:Osteocalcin; C071482:calpeptin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D048490:raf Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D018631:ras Proteins; D002117:Calcitriol; C032881:lysophosphatidic acid; D015739:Nocodazole; D003078:Colchicine