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TGF-β and BMP Signaling Pathways in Skeletal Dysplasia with Short and Tall Stature

Alice Costantini1,2, Alessandra Guasto1, Valérie Cormier-Daire1,3

  • 1Paris Cité University, INSERM UMR 1163, Institut Imagine, Paris, France; email: alice.costantini@institutimagine.org, alessandra.guasto@institutimagine.org, valerie.cormier-daire@inserm.fr.

Annual Review of Genomics and Human Genetics
|August 25, 2023
PubMed

Insights

Genetic variants in transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) pathways cause skeletal dysplasias, affecting stature. This review details advances in understanding these conditions and potential therapeutic targets.

Area of Science:

  • Genetics
  • Molecular Biology
  • Developmental Biology

Background:

  • Transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling are crucial for skeletal development and health.
  • Over 30 skeletal dysplasias are linked to genetic variants in TGF-β superfamily genes or regulators of TGF-β/BMP bioavailability.

Purpose of the Study:

  • To review recent advancements in understanding skeletal dysplasias caused by impaired TGF-β/BMP signaling.
  • To discuss conditions resulting in short stature (acromelic dysplasia, cardiospondylocarpofacial syndrome) and tall stature (Marfan syndrome).

Main Methods:

  • Review of clinical features and genetic findings in patients.
  • Analysis of pathomolecular mechanisms using patient-derived fibroblasts and mouse models.
  • Discussion of emerging therapeutic strategies targeting TGF-β signaling.

Main Results:

  • Pathogenic variants in TGF-β/BMP pathway genes lead to diverse skeletal dysplasias.
  • Detailed understanding of genetic basis and molecular mechanisms for specific conditions.
  • Progress in developing drugs targeting TGF-β signaling.

Conclusions:

  • Impaired TGF-β/BMP signaling is a significant cause of skeletal dysplasias with varying stature outcomes.
  • Further research into pathomolecular mechanisms is essential for therapeutic development.
  • Advances in TGF-β targeting drugs offer future treatment possibilities.
Keywords:
BMPTGF-βshort statureskeletal dysplasiatall stature

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