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Mice lacking smooth muscle calponin display increased bone formation that is associated with enhancement of bone morphogenetic protein responses
Author(s) -
Yoshikawa Hideki,
Taniguchi Shunichiro,
Yamamura Hisako,
Mori Shigeki,
Sugimoto Mizuo,
Miyado Kenji,
Nakamura Kenji,
Nakao Kazuki,
Katsuki Motoya,
Shibata Nobuhiko,
Takahashi Katsuhito
Publication year - 1998
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.1998.00214.x
Subject(s) - calponin , bone morphogenetic protein , biology , microbiology and biotechnology , bone morphogenetic protein 2 , actin , cartilage , medicine , endocrinology , in vitro , anatomy , biochemistry , gene
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.