Proliferation, Osteogenic Differentiation, and FGF-2 Modulation of Posterofrontal/Sagittal Suture–Derived Mesenchymal Cells In Vitro

Sonic Hedgehog Influences the Balance of Osteogenesis and Adipogenesis in Mouse Adipose-Derived Stromal Cells

“…Alkaline phosphatase (ALP) staining and quantification was performed from 0 to 14 days of differentiation, as previously described. 18 Total ALP activity was assayed by measuring the p-nitrophenol formed from the enzymatic hydrolysis of p-nitrophenylphosphate, which was normalized to total protein quantity (Pierce). Alizarin red (AR) staining was performed from 0 to 14 days of differentiation.…”

Craniomaxillofacial Sources of Mesenchymal Stem Cells: A Brief Review

“…Both TGF-β1 and TGF-β3 will also induce expression of fibroblastic growth factors (FGF-2, FGF-18) and cytokines associated with posterofrontal suture fusion [48] . Consistent with the pro-chondrogenic anti-osteogenic effects of TGF-β1, posterofrontal SMC express higher levels of FGF-2 [6] , which severely reduces osteogenesis (downregulated of Col I) [47] while stimulating a dose-dependent upregulation of Sox9 and OB-cadherin, indicative of a chondrogenic fate [47] . Bone morphogenetic protein (BMP) also plays a role in determining suture fate since it is implicated in ectopic bone formation [49] .…”

“…However, they differ in that posterofrontal SMCs have been reported to express significantly higher levels of Osteopontin (Opn) [6] , Runx2, Col Iα and Alkaline phosphatase (ALP) activity [46] . With generally higher levels of bone nodule formation [47] , posterofrontal SMC demonstrate greater osteogenic potential than sagittal SMC. Furthermore, compared to their sagittal-derived counterparts, posterofrontal SMC show elevated expression of Collagen II (Col II), a chondrogenic component of the extracellular matrix [6] , thus indicating greater chondrogenic potential.…”

“…Transforming growth factor (TGF)-β is known to control cell growth, proliferation and differentiation, so it has an expected involvement in SMC. Interestingly, SMC derived from posterofrontal suture of postnatal mice show approximately five times the expression level of TGF-β1 than sagittal suture [6,46,47] . TGF-β1 has been shown to not only upregulate chondrogenic marker expression in posterofrontal SMC [46] , but also significantly downregulates proliferation and osteogenic differentiation of both populations, whereas TGF-3 significantly increases posterofrontal SMC proliferation [48] .…”

Craniosynostosis

“…Differences in FGF signaling, TGF-β signaling, and Hedgehog signaling have been identified using the murine model. [53][54][55][56][57] In addition, Warren et al demonstrated that inhibitors of BMP signaling such as Noggin play a pivotal role in the differential fate of the murine PF suture. High FGF-2 activity in the PF suture was found to downregulate noggin expression at dominant inheritance, RAB-23 mutations instead result in autosomal recessive transmission for craniosynostosis with Carpenter syndrome.…”