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Culture of Murine Embryonic Metatarsals: A Physiological Model of Endochondral Ossification
Published on: December 3, 2016
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Smpd3 Expression in both Chondrocytes and Osteoblasts Is Required for Normal Endochondral Bone Development.
Jingjing Li1, Garthiga Manickam2, Seemun Ray2
1Department of Medicine, McGill University, Montreal, Quebec, Canada.
Molecular and Cellular Biology
|June 22, 2016
Summary
Sphingomyelin phosphodiesterase 3 (SMPD3) is crucial for skeletal development. Its deficiency causes severe bone deformities, highlighting SMPD3
Area of Science:
- Biochemistry
- Genetics
- Developmental Biology
Background:
- Sphingomyelin phosphodiesterase 3 (SMPD3) is a lipid-metabolizing enzyme vital for skeletal development.
- Loss-of-function mutations in SMPD3, termed fragilitas ossium (fro), lead to impaired bone and cartilage mineralization and congenital skeletal deformities.
Purpose of the Study:
- To investigate the regulatory mechanisms of SMPD3 expression during chondrogenesis.
- To determine the specific roles of SMPD3 in chondrocytes and osteoblasts in endochondral bone development.
Main Methods:
- Investigated the regulation of Smpd3 expression by parathyroid hormone-related peptide (PTHrP) and SOX9 in ATDC5 chondrogenic cells.
- Utilized transgenic mice with Smpd3 overexpression in chondrocytes of fro/fro mice.
- Generated Smpd3(flox/flox) mice for conditional gene inactivation using the Cre-loxP system.
- Analyzed skeletal phenotypes of Smpd3(flox/flox); Osx-Cre and Smpd3(flox/flox); Col2a1-Cre mice.
Main Results:
- Parathyroid hormone-related peptide downregulates Smpd3 expression via SOX9 in chondrogenic cells.
- Transgenic Smpd3 expression in fro/fro mouse chondrocytes corrected cartilage defects but not bone abnormalities.
- Conditional ablation of Smpd3 in chondrocytes (Smpd3(flox/flox); Col2a1-Cre) mimicked the cartilage phenotype of fro/fro mice.
- Ablation of Smpd3 in both chondrocytes and osteoblasts (Smpd3(flox/flox); Osx-Cre) recapitulated the severe skeletal phenotype of fro/fro mice.
Conclusions:
- Smpd3 expression is regulated by PTHrP and SOX9 during chondrogenesis.
- Smpd3 function in chondrocytes is essential for cartilage development.
- Smpd3 expression in both chondrocytes and osteoblasts is indispensable for normal endochondral bone formation.
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