RESEARCH SUPPORT, NON-U.S. GOV'T
Add like
Add dislike
Add to saved papers

Apert syndrome mutant FGFR2 and its soluble form reciprocally alter osteogenesis of primary calvarial osteoblasts.

Apert syndrome is characterized by craniosynostosis and syndactyly, and is predominantly caused by mutation of either S252W or P253W in the fibroblast growth factor receptor (FGFR) 2 gene. In this study, we characterized the effects of one of the mutations (S252W) using primary calvarial osteoblasts derived from transgenic mice, Ap-Tg and sAp-Tg, that expressed an Apert-type mutant FGFR2 (FGFR2IIIc-S252W; FGFR2IIIc-Ap), and the soluble form (extracellular domain only) of the mutant FGFR2 (sFGFR2IIIc-Ap), respectively. Compared to WT-derived osteoblasts, osteoblasts from Ap-Tg mouse showed a higher proliferative activity and enhanced differentiation, while those from sAp-Tg mouse exhibited reduced potential for proliferation and osteogenic differentiation. When transplanted with β-tricalcium phosphate (β-TCP) granules into immunodeficient mice, Ap-Tg-derived osteoblasts showed a higher bone forming capacity, whereas sAp-Tg-derived osteoblasts were completely deficient for this phenotype. Phosphorylation of extracellular signal-regulated kinase (ERK), MEK, PLCγ, and p38 was increased in Ap-Tg-derived osteoblasts, whereas phosphorylation of these signaling molecules was reduced in sAp-Tg-derived osteoblasts. Interestingly, when these experiments were carried out using osteoblasts from the mice generated by crossing Ap-Tg and sAp-Tg (Ap/sAp-Tg), which co-expressed FGFR2IIIc-Ap and sFGFR2IIIc-Ap, the results were comparable to those obtained from WT-derived osteoblasts. Taken together, these results indicate that osteoblasts expressing FGFR2IIIc-Ap proliferate and differentiate via highly activated MEK, ERK, and p38 pathways, while these pathways are suppressed in osteoblasts expressing sFGFR2IIIc-Ap. Our findings also suggest that altered FGFR2IIIc signaling in osteoblasts is mostly responsible for the phenotypes seen in Apert syndrome, therefore these osteoblast cell lines are useful tools for investigating the pathogenesis of Apert syndrome.

Full text links

For the best experience, use the Read mobile app

Group 7SearchHeart failure treatmentPapersTopicsCollectionsEffects of Sodium-Glucose Cotransporter 2 Inhibitors for the Treatment of Patients With Heart Failure Importance: Only 1 class of glucose-lowering agents-sodium-glucose cotransporter 2 (SGLT2) inhibitors-has been reported to decrease the risk of cardiovascular events primarily by reducingSeptember 1, 2017: JAMA CardiologyAssociations of albuminuria in patients with chronic heart failure: findings in the ALiskiren Observation of heart Failure Treatment study.CONCLUSIONS: Increased UACR is common in patients with heart failure, including non-diabetics. Urinary albumin creatininineJul, 2011: European Journal of Heart FailureRandomized Controlled TrialEffects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.Review

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

Read by QxMD is copyright © 2021 QxMD Software Inc. All rights reserved. By using this service, you agree to our terms of use and privacy policy.

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app