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Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
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Nemo-like kinase regulates postnatal skeletal homeostasis
Ernesto Canalis1, Lauren Kranz, Stefano Zanotti
1Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut; The University of Connecticut School of Medicine, Farmington, Connecticut.
Journal of Cellular Physiology
|March 26, 2014
Summary
Nemo-like kinase (Nlk) suppresses bone formation. Inactivating Nlk in developing osteoblasts increased bone volume by reducing osteoclast and osteoblast activity, suggesting Nlk regulates skeletal homeostasis.
Area of Science:
- Skeletal Biology
- Molecular Endocrinology
- Bone Physiology
Background:
- Nemo-like kinase (Nlk), a mitogen-activated protein kinase, influences osteoblastogenesis.
- In vitro studies show Nlk suppresses osteoblastogenesis, but its in vivo skeletal role remains unclear.
Purpose of the Study:
- To investigate the in vivo function of Nlk in skeletal homeostasis.
- To determine the consequences of Nlk inactivation in osteoblasts.
Main Methods:
- Generation of Nlk conditional knockout mice using Nlk(loxP/loxP) and Cre-driver lines (Prx1-Cre, Osx-Cre, Bglap-Cre).
- Skeletal phenotyping and bone histomorphometry analysis at various ages.
- Analysis of osteoprotegerin mRNA expression.
Main Results:
- Osx-Cre;Nlk(Δ/Δ) mice showed increased trabecular bone volume due to higher trabecular number.
- Histomorphometry revealed reduced osteoclast numbers and eroded surfaces in males, and decreased osteoblast numbers and function in females.
- Increased osteoprotegerin mRNA expression was observed, correlating with reduced osteoclast and osteoblast populations.
Conclusions:
- Nlk acts as a negative regulator of skeletal homeostasis when expressed in undifferentiated osteoblasts.
- Nlk inactivation impacts osteoclastogenesis and bone resorption, influencing skeletal development.
- Conditional deletion in mature osteoblasts (Bglap-Cre) did not yield a skeletal phenotype, indicating a role in earlier osteoblast differentiation stages.
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