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Mice lacking smooth muscle calponin display increased bone formation that is associated with enhancement of bone
H Yoshikawa1, S I Taniguchi, H Yamamura
1Department of Orthopaedic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Osaka 537-8511, Japan.
Background:
Calponin is a calmodulin-and actin-binding protein expressed in smooth muscle. It promotes actin polymerization and inhibits actin-activated myosin ATPase activity. Despite the molecular and functional characterization of calponin in vitro, the physiological role of calponin in vivo has not been clarified.
Results:
We investigated the in vivo function of smooth muscle calponin (also called basic calponin or calponin h1) by generating mice carrying a targeted mutation in both alleles of the calponin gene. Mice lacking basic calponin expression displayed enhanced ectopic bone formation in vivo, induced by recombinant human bone morphogenetic protein-2 (rhBMP-2), and an augmentation of the degree of osteoblastic differentiation of embryonic mesenchymal cells when they were stimulated by rhBMP-2. Basic calponin messenger RNA was shown to be expressed in developing and healing bone tissues, and in undifferentiated MC3T3-E1 osteoblasts. An examination of the skeletons of mutated mice showed an early onset of cartilage formation and ossification, and increased postnatal bone formation characterized by an increase in the number of activated periosteal osteoblasts. Bone fracture healing was accelerated in mutated mice.
Conclusion:
This is the first demonstration of animals with enhanced BMP responsiveness in host cells, suggesting that endogenous basic calponin may play a negative role in an osteogenic programme.
Insights
Mice lacking smooth muscle calponin showed increased bone formation and accelerated fracture healing. This suggests calponin negatively regulates bone development and repair processes.
Area of Science:
- Biochemistry
- Molecular Biology
- Skeletal Biology
Background:
- Calponin is a calmodulin- and actin-binding protein found in smooth muscle.
- It influences actin polymerization and myosin ATPase activity.
- Its in vivo physiological role remains unclear.
Purpose of the Study:
- To investigate the in vivo function of smooth muscle calponin (basic calponin/calponin h1).
- To determine calponin's role in bone formation and healing.
Main Methods:
- Generation of mice with a targeted mutation in both alleles of the calponin gene.
- Assessment of bone formation in response to recombinant human bone morphogenetic protein-2 (rhBMP-2).
- Analysis of skeletal development, osteoblast differentiation, and fracture healing in mutant mice.
Main Results:
- Mice lacking basic calponin exhibited enhanced ectopic bone formation induced by rhBMP-2.
- Increased osteoblastic differentiation of mesenchymal cells was observed.
- Mutant mice showed accelerated cartilage formation, ossification, increased postnatal bone formation, and faster bone fracture healing.
Conclusions:
- This study demonstrates enhanced bone morphogenetic protein (BMP) responsiveness in cells lacking calponin.
- Endogenous basic calponin appears to play a negative regulatory role in osteogenesis.
- These findings provide novel insights into the molecular mechanisms of bone formation and repair.