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Inactivation of Fam20B in Joint Cartilage Leads to Chondrosarcoma and Postnatal Ossification Defects

Pan Ma1,2, Wenjuan Yan1, Ye Tian1

  • 1Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas, United States of America.

Scientific Reports
|July 14, 2016
PubMed

Insights

Inactivating FAM20B, crucial for proteoglycan formation, caused bone defects and chondrosarcoma in mice. This highlights proteoglycans

Area of Science:

  • Skeletal biology
  • Cellular biology
  • Biochemistry

Background:

  • Proteoglycans are crucial for chondrocyte proliferation and differentiation during endochondral ossification.
  • FAM20B (Family with sequence similarity 20 member-B) is a xylose kinase essential for glycosaminoglycan (GAG) formation in proteoglycans.
  • The role of FAM20B in skeletal development is not fully understood.

Purpose of the Study:

  • To investigate the function of FAM20B in postnatal endochondral ossification.
  • To elucidate the molecular mechanisms by which FAM20B regulates chondrocyte differentiation and proliferation.

Main Methods:

  • Conditional inactivation of FAM20B in dental mesenchyme using Osr2-Cre mice.
  • Analysis of skeletal phenotypes, including ossification and chondrosarcoma formation.
  • Mechanistic studies involving signaling pathway analysis (WNT, BMP, PTHrP/IHH).

Main Results:

  • Conditional inactivation of FAM20B led to chondrosarcoma in the knee joint and severe defects in postnatal ossification of long bones.
  • FAM20B deficiency resulted in dysregulated WNT, BMP, and PTHrP/IHH signaling pathways in epiphyseal chondrocytes.
  • Inhibition of WNT signaling partially rescued the bone defects in the mutant mice.

Conclusions:

  • FAM20B-catalyzed proteoglycans are critical for maintaining signaling balance during chondrocyte differentiation and proliferation.
  • FAM20B plays a vital role in postnatal endochondral ossification, partly through the regulation of WNT signaling.

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