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Published on: January 30, 2014
Twisted gastrulation, a bone morphogenetic protein agonist/antagonist, is not required for post-natal skeletal
Elisabetta Gazzerro1, Valerie Deregowski, Lisa Stadmeyer
1Department of Research, Saint Francis Hospital and Medical Center, Hartford, CT 06105-1299, USA.
Twisted gastrulation (Tsg) enhances bone morphogenetic protein (BMP) activity in osteoblasts. However, Tsg plays a minimal role in maintaining adult bone homeostasis in vivo.
Area of Science:
- Skeletal Biology
- Molecular Endocrinology
- Bone Physiology
Background:
- Twisted gastrulation (Tsg) is a secreted glycoprotein modulating bone morphogenetic protein (BMP) signaling.
- Tsg's role in adult bone homeostasis and osteoblast function remains largely unknown.
- Tsg exhibits context-dependent BMP agonist and antagonist activities.
Purpose of the Study:
- To investigate the in vivo and in vitro functions of Tsg in adult bone.
- To determine the consequences of Tsg deletion on skeletal development and osteoblast activity.
- To elucidate Tsg's role in BMP-mediated signaling within the bone microenvironment.
Main Methods:
- Generation and analysis of tsg null mice.
- Assessment of skeletal phenotypes, including bone volume and cellularity.
- In vitro studies using primary osteoblasts from tsg null and wild-type mice.
- RNA interference to down-regulate Tsg expression in osteoblasts.
Main Results:
- Tsg null mice exhibited a transient 40% decrease in trabecular bone volume at 4 weeks.
- Osteoblast and osteoclast numbers, bone formation, and resorption rates were unaffected.
- Tsg deficiency impaired BMP-2-stimulated osteocalcin expression and alkaline phosphatase activity in osteoblasts.
- Tsg null osteoblasts showed reduced BMP signaling, confirming Tsg's role in enhancing BMP activity.
Conclusions:
- Endogenous Tsg is essential for optimal BMP activity in osteoblastic cells in vitro.
- Tsg plays a minor role in the regulation of adult bone homeostasis in vivo.
- The transient skeletal phenotype suggests compensatory mechanisms in adult bone.
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