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

• Published in: Molecular and cellular biochemistry Vol. 436; no. 1-2; pp. 111 - 117
• Main Authors: da Costa Fernandes, Celio J., do Nascimento, Augusto Santana, da Silva, Rodrigo A., Zambuzzi, Willian F.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2017; Springer; Springer Nature B.V
• Subjects: Alkaline phosphatase; Animals; Biochemistry; Biocompatibility; Biomedical and Life Sciences; Biomedical materials; Bone diseases; Calcification, Physiologic; Cardiology; Cell Differentiation; Coculture Techniques; Crosstalk; Differentiation; Etiology; Extracellular signal-regulated kinase; Fibroblasts; Fibroblasts - cytology; Fibroblasts - metabolism; Genetic aspects; Genotype & phenotype; Hedgehog protein; Hedgehog Proteins - metabolism; Hostages; Immunoblotting; Life Sciences; MAP kinase; MAP Kinase Signaling System - physiology; Medical Biochemistry; Metabolism; Mice; Mineralization; NIH 3T3 Cells; Oncology; Osteoblastogenesis; Osteoblasts; Osteoblasts - cytology; Osteoblasts - metabolism; Paracrine Communication; Paracrine signalling; Patched protein; Phosphatases; Phosphorylation; Proteins; Rac1 protein; Transducers; Trophic factors; Osteoblast; Bone; Fibroblast; Crosstalk; Cell signaling
• ISSN: 0300-8177; 1573-4919; 1573-4919
• DOI: 10.1007/s11010-017-3083-0

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.