title: Overexpression of H1 calponin in osteoblast lineage cells leads to a decrease in bone mass by disrupting osteoblast function and promoting osteoclast formation.
abstract: H1 calponin (CNN1) is known as a smooth muscle-specific, actin-binding protein which regulates smooth muscle contractive activity. Although previous studies have shown that CNN1 has effect on bone, the mechanism is not well defined. To investigate the role of CNN1 in maintaining bone homeostasis, we generated transgenic mice overexpressing Cnn1 under the control of the osteoblast-specific 3.6-kb Col1a1 promoter. Col1a1-Cnn1 transgenic mice showed delayed bone formation at embryonic stage and decreased bone mass at adult stage. Morphology analyses showed reduced trabecular number, thickness and defects in bone formation. The proliferation and migration of osteoblasts were decreased in Col1a1-Cnn1 mice due to alterations in cytoskeleton. The early osteoblast differentiation of Col1a1-Cnn1 mice was increased, but the late stage differentiation and mineralization of osteoblasts derived from Col1a1-Cnn1 mice were significantly decreased. In addition to impaired bone formation, the decreased bone mass was also associated with enhanced osteoclastogenesis. Tartrate-resistant acid phosphatase (TRAP) staining revealed increased osteoclast numbers in tibias of 2-month-old Col1a1-Cnn1 mice, and increased numbers of osteoclasts co-cultured with Col1a1-Cnn1 osteoblasts. The ratio of RANKL to OPG was significantly increased in Col1a1-Cnn1 osteoblasts. These findings reveal a novel function of CNN1 in maintaining bone homeostasis by coupling bone formation to bone resorption.
authors.affiliation: Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Su
authors.forename: Maomao
authors.initials: M
authors.lastname: Chen
authors.forename: Siyu
authors.initials: S
authors.lastname: Chen
authors.forename: Can
authors.initials: C
authors.lastname: Li
authors.forename: Yangli
authors.initials: Y
authors.lastname: Xie
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yaozong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.forename: Qifen
authors.initials: Q
authors.lastname: He
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Du
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D001483:Base Sequence; D001696:Biomechanical Phenomena; D001846:Bone Development; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D018920:Coculture Techniques; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D017931:DNA Primers; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010024:Osteoporosis / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D000096985:Calponins
chemical_list: D002135:Calcium-Binding Proteins; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D017931:DNA Primers; D008840:Microfilament Proteins; D000096985:Calponins