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Journal article
Role of cholesterol in the regulation of growth plate chondrogenesis and longitudinal bone growth
The Journal of biological chemistry, v 279(6), pp 4642-4647
06 Feb 2004
PMID: 14612457
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Inborn errors of cholesterol synthesis are associated with multiple systemic abnormalities, including skeletal malformations. The regulatory role of cholesterol during embryogenesis appears to be mediated by Shh, a signaling molecule in which activity depends on molecular events involving cholesterol. Based on this evidence, we hypothesized that cholesterol, by modifying the activity of Ihh (another of the Hedgehog family proteins) in the growth plate, regulates longitudinal bone growth. To test this hypothesis, we treated rats with AY 9944, an inhibitor of the final reaction of cholesterol synthesis. After 3 weeks, AY 9944 reduced the cumulative growth, tibial growth, and the tibial growth plate height of the rats. To determine whether cholesterol deficiency affects bone growth directly at the growth plate, we then cultured fetal rat metatarsal bones in the presence of AY 9944. After 4 days, AY 9944 suppressed metatarsal growth and growth plate chondrocyte proliferation and hypertrophy. The inhibitory effect on chondrocyte hypertrophy was confirmed by the AY 9944-mediated decreased expression of collagen X. Lastly, AY 9944 decreased the expression of Ihh in the metatarsal growth plate. We conclude that reduced cholesterol synthesis in the growth plate, possibly by altering the normal activity of Ihh, results in suppressed longitudinal bone growth and growth plate chondrogenesis.
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Details
- Title
- Role of cholesterol in the regulation of growth plate chondrogenesis and longitudinal bone growth
- Creators
- Shufang Wu - St. Christopher's Hospital for ChildrenFrancesco De Luca - St. Christopher's Hospital for ChildrenFrancesco DeLuca - Pediatrics
- Publication Details
- The Journal of biological chemistry, v 279(6), pp 4642-4647
- Publisher
- ASBMB Publications / Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics; College of Medicine
- Web of Science ID
- WOS:000188554300086
- Scopus ID
- 2-s2.0-1042266622
- Other Identifier
- 991019168031904721
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Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology