Profilin1 Regulates Sternum Development and Endochondral Bone Formation

• Published in: The Journal of biological chemistry Vol. 287; no. 40; pp. 33545 - 33553
• Main Authors: Miyajima, Daisuke, Hayata, Tadayoshi, Suzuki, Takafumi, Hemmi, Hiroaki, Nakamoto, Tetsuya, Notomi, Takuya, Amagasa, Teruo, Böttcher, Ralph T., Costell, Mercedes, Fässler, Reinhard, Ezura, Yoichi, Noda, Masaki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28-09-2012; American Society for Biochemistry and Molecular Biology
• Subjects: Alleles; Animals; Bone; Bone and Bones - metabolism; Bone Morphogenetic Protein (BMP); Cartilage; Cartilage - metabolism; Cartilage Biology; Cell Movement; Cytoskeleton; Cytoskeleton - metabolism; Development; Developmental Biology; Gene Expression Regulation, Developmental; Genotype; Mesenchymal Stem Cells - cytology; Mice; Mice, Knockout; Mice, Transgenic; NIH 3T3 Cells; Osteoblasts - cytology; Osteogenesis; Profilins - metabolism; Profilins - physiology; RNA, Small Interfering - metabolism; Time Factors; Transfection; X-Ray Microtomography - methods; Development; Bone Morphogenetic Protein (BMP); Cartilage; Cytoskeleton; Bone; Cartilage Biology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M111.329938

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
Background: Profilin1 is required for actin cytoskeletal modulation.
Results: Mice lacking Profilin1 in mesenchymal progenitor cells exhibit cleft sternum and delay in endochondral bone formation. Profilin1 inactivation in skeletal cells reduces motile function of skeletal cells.
Conclusion: Profilin1 regulates skeletal development and facilitates skeletal cell migration.
Significance: Our findings provide new insights into skeletal development based on cytoskeletal function.