Fibroblast contributes for osteoblastic phenotype in a MAPK-ERK and sonic hedgehog signaling-independent manner

被引:0
作者
Celio J. da Costa Fernandes
Augusto Santana do Nascimento
Rodrigo A. da Silva
Willian F. Zambuzzi
机构
[1] Bioscience Institute,Bioassays and Cell Dynamics Lab, Department of Chemistry and Biochemistry
[2] UNESP,undefined
来源
Molecular and Cellular Biochemistry | 2017年 / 436卷
关键词
Bone; Fibroblast; Osteoblast; Crosstalk; Cell signaling;
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学科分类号
摘要
We hypothesized that a crosstalk between osteoblast and fibroblast (FB) exists, which contributes to bone as a dynamic tissue. Cell-free supernatants were harvested from fibroblast cultures and later subject pre-osteoblasts to investigate there capacity to modulate cell viability and differentiation mechanisms, reporting the possible involvement of Shh signaling as a paracrine mechanism. By exploring immunoblotting technology, we have shown that FB-released factors interfere with osteoblast metabolism by up-regulating the phosphorylation of FAK and Rac-1 proteins at the early stage and later contribute to osteoblast differentiation by up-modulating alkaline phosphatase (ALP) and in vitro mineralization. We also found that Shh signaling was not required during osteoblastic differentiation promoted by the FB-released factors as well as MAPK-ERK phosphorylation, while pre-osteoblast cultures subjected to osteogenic medium (O.M.) require downstream transducers of Shh, such as Patched and Gli-1, and MAPK-ERK. Altogether, our results indicate for the first time a possible mechanism involved in the crosstalk between fibroblasts and osteoblasts, as it was possible to observe trophic factors released by fibroblasts interfering decisively in osteoblast metabolism in a Shh-independent manner. This study collaborates the body of work that indicates paracrine signaling molecules participate in the crosstalk among bone-resident cells and explains, at least partially, the biological mechanisms responsible for bone tissue dynamism, opening new avenues to understand etiologies of bone diseases.
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页码:111 / 117
页数:6
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共 104 条
[1]  
Ap Kusumbe(2014)Coupling Of angiogenesis and osteogenesis by a specific vessel subtype in bone Nature 507 323-328
[2]  
Sk Ramasamy(2015)Regulation of tissue morphogenesis by endothelial cell-derived signals Trends Cell Biol 25 148-157
[3]  
Adams Rh(2011)Crosstalk between cartilage and bone: when bone cytokines matter Cytokine Growth Factor Rev 22 91-97
[4]  
Sk Ramasamy(2015)Bone and muscle: interactions beyond mechanical Bone 80 109-114
[5]  
Ap Kusumbe(2014)Kinome profiling of osteoblasts on hydroxyapatite opens new avenues on biomaterial cell signaling Biotechnol Bioeng 111 1900-1905
[6]  
Adams Rh(2000)The osteoblast: a sophisticated fibroblast under central surveillance Science 289 1501-1504
[7]  
Funck-Brentano T(1997)Missense mutations abolishing dna binding of the osteoblast-specific transcription factor Osf2/Cbfa1 in cleidocranial dysplasia Nat Genet 16 307-310
[8]  
Cohen-Solal M(1996)Increased bone formation in osteocalcin-deficient mice Nature 382 448-452
[9]  
Brotto M(1997)Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation Cell 89 747-754
[10]  
Bonewald L(2014)Bone morphogenetic proteins: structure, biological function and therapeutic applications Arch Biochem Biophys 561 64-73