title: Profilin1 regulates sternum development and endochondral bone formation.
abstract: Bone development is a dynamic process that requires cell motility and morphological adaptation under the control of actin cytoskeleton. This actin cytoskeleton system is regulated by critical modulators including actin-binding proteins. Among them, profilin1 (Pfn1) is a key player to control actin fiber structure, and it is involved in a number of cellular activities such as migration. During the early phase of body development, skeletal stem cells and osteoblastic progenitor cells migrate to form initial rudiments for future skeletons. During this migration, these cells extend their process based on actin cytoskeletal rearrangement to locate themselves in an appropriate location within microenvironment. However, the role of Pfn1 in regulation of mesenchymal progenitor cells (MPCs) during skeletal development is incompletely understood. Here we examined the role of Pfn1 in skeletal development using a genetic ablation of Pfn1 in MPCs by using Prx1-Cre recombinase. We found that Pfn1 deficiency in MPCs caused complete cleft sternum. Notably, Pfn1-deficient mice exhibited an absence of trabecular bone in the marrow space of appendicular long bone. This phenotype is location-specific, as Pfn1 deficiency did not largely affect osteoblasts in cortical bone. Pfn1 deficiency also suppressed longitudinal growth of long bone. In vitro, Pfn1 deficiency induced retardation of osteoblastic cell migration. These observations revealed that Pfn1 is a critical molecule for the skeletal development, and this could be at least in part associated with the retardation of cell migration.
authors: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Daisuke
authors: D
authors: Miyajima
authors: Tadayoshi
authors: T
authors: Hayata
authors: Takafumi
authors: T
authors: Suzuki
authors: Hiroaki
authors: H
authors: Hemmi
authors: Tetsuya
authors: T
authors: Nakamoto
authors: Takuya
authors: T
authors: Notomi
authors: Teruo
authors: T
authors: Amagasa
authors: Ralph T
authors: RT
authors: Böttcher
authors: Mercedes
authors: M
authors: Costell
authors: Reinhard
authors: R
authors: Fässler
authors: Yoichi
authors: Y
authors: Ezura
authors: Masaki
authors: M
authors: Noda
mesh_terms: D000483:Alleles; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002356:Cartilage / Q000378:metabolism; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis; D051304:Profilins / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D051304:Profilins; D034741:RNA, Small Interfering