Mice lacking smooth muscle calponin display increased bone formation that is associated with enhancement of bone morphogenetic protein responses.
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.


CONCLUSIONS
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.
Yoshikawa
H
H
Department of Orthopaedic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Osaka 537-8511, Japan.
Taniguchi
S I
SI
Yamamura
H
H
Mori
S
S
Sugimoto
M
M
Miyado
K
K
Nakamura
K
K
Nakao
K
K
Katsuki
M
M
Shibata
N
N
Takahashi
K
K
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D001842:Bone and Bones / Q000196:embryology / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D005269:Femur; D017102:Fracture Healing; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D015151:Immunoblotting; D017403:In Situ Hybridization; D051379:Mice; D008840:Microfilament Proteins; D009130:Muscle, Smooth / Q000737:chemistry / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta; D000096985:Calponins
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D016212:Transforming Growth Factor beta; D000096985:Calponins; C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse