Osteogenesis requires FAK‐dependent collagen synthesis by fibroblasts and osteoblasts
| Autor: | Christopher A. McCulloch, Dhaarmini Rajshankar, Yongqiang Wang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Mutant Core Binding Factor Alpha 1 Subunit Biochemistry Collagen Type I Focal adhesion Mice 03 medical and health sciences Calcification Physiologic 0302 clinical medicine Osteogenesis Conditional gene knockout Genetics Animals Molecular Biology Transcription factor Cells Cultured Gene knockdown Osteoblasts Chemistry Transfection Fibroblasts Cell biology RUNX2 030104 developmental biology Protein kinase domain Sp7 Transcription Factor Focal Adhesion Kinase 1 030220 oncology & carcinogenesis biological phenomena cell phenomena and immunity Transcription Factors Biotechnology |
| Zdroj: | The FASEB Journal. 31:937-953 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.201600645r |
| Popis: | Focal adhesion kinase (FAK) is critical in adhesion-dependent signaling, but its role in osteogenesis in vivo is ill defined. We deleted Fak in fibroblasts and osteoblasts in Floxed-Fak mice bred with those expressing Cre-recombinase driven by 3.6-kb α1(I)-collagen promoter. Compared with wild-type (WT), conditional FAK-knockout (CFKO) mice were shorter (2-fold; P 3-fold less than WT, respectively. Disruptions of FAK function in osteoblasts by conditional knockout, siRNA-knockdown, or FAK inhibitor reduced mRNA and protein expression of Runx2 (>30%), Osterix (>25%), and collagen-1 (2-fold). Collagen synthesis was abrogated in WT osteoblasts with Runx2 knockdown and in Fak-null fibroblasts transfected with an FAK kinase domain mutant or a kinase-impaired mutant (Y397F). These data indicate that FAK regulates osteogenesis through transcription factors that regulate collagen synthesis.-Rajshankar, D., Wang, Y., McCulloch, C. A. Osteogenesis requires FAK-dependent collagen synthesis by fibroblasts and osteoblasts. |
| Databáze: | OpenAIRE |
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