title: Profilin1 is expressed in osteocytes and regulates cell shape and migration.
abstract: Osteocytes are the most abundant cells in bone and regulate bone metabolism in coordination with osteoblasts and osteoclasts. However, the molecules that control osteocytes are still incompletely understood. Profilin1 is an actin-binding protein that is involved in actin polymerization. Osteocytes possess characteristic dendritic process formed based on actin cytoskeleton. Here, we examined the expression of profilin1 and its function in osteocytes. Profilin1 mRNA was expressed in osteocytic MLO-Y4 cells and its levels were gradually increased along with the time in culture. With regard to functional aspect, knockdown of profilin1 by siRNA enhanced BMP-induced increase in alkaline phosphatase expression levels in MLO-Y4 cells. Profilin1 knockdown suppressed the levels of dendritic processes and migration of MLO-Y4 cells. Since aging causes an increase in ROS in the body, we further examined the effects of hydrogen peroxide on the expression of profilin1. Hydrogen peroxide treatment increased the levels of profilin1 mRNA in MLO-Y4 cells in contrast to the decline in alkaline phosphatase. Profilin1 was expressed not only in MLO-Y4cells but also in the primary cultures of osteocytes. Importantly, profilin1 mRNA levels in primary cultures of osteocytes were higher than those in primary cultures of osteoblasts. To examine in vivo role of profilin1 in osteocytes, profilin1 was conditionally knocked out by using DMP1-cre and profilin1 floxed mice. This conditional deletion of profilin1 specifically in osteocytes resulted in reduction in the levels of bone volume and bone mineral density. These data indicate that profilin1 is expressed in osteocytes and regulates cell shape, migration and bone mass.
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.|Department of Maxillofacial Orthognathics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Wanting
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Izu
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Arayal
authors.initials: A
authors.lastname: Smriti
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Makiri
authors.initials: M
authors.lastname: Kawasaki
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Chantida
authors.initials: C
authors.lastname: Pawaputanon
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Böttcher
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Costell
authors.affiliation: Department of Maxillofacial Orthognathics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Moriyama
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.|Yokohama City Minato Red Cross Hospital, Yokohama, Kanagawa, Japan.|Department of Orthopedic Surgery, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masaki
authors.identifier: http://orcid.org/0000-0002-9710-4601
authors.initials: M
authors.lastname: Noda
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ezura
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015519:Bone Density; D016723:Bone Remodeling; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D005838:Genotype; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010011:Osteocytes / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D061251:Primary Cell Culture; D051304:Profilins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D055114:X-Ray Microtomography
chemical_list: C495739:Pfn1 protein, mouse; D051304:Profilins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D000469:Alkaline Phosphatase
keywords: BMP; osteocyte; profilin