title: RELAXIN enhances differentiation and matrix mineralization through Relaxin/insulin-like family peptide receptor 2 (Rxfp2) in MC3T3-E1 cells in vitro.
abstract: RELAXIN (RLN) is a polypeptide hormone of the insulin-like hormone family; it facilitates birth by softening and widening the pubic symphysis and cervix in many mammals, including humans. The role of RLN in bone metabolism was recently suggested by its ability to induce osteoclastogenesis and activate osteoclast function. RLN binds to RELAXIN/INSULIN-LIKE FAMILY PEPTIDE 1 (RXFP1) and 2 (RXFP2), with varying species-specific affinities. Young men with mutated RXFP2 are at high risk for osteoporosis, as RXFP2 influences osteoblast metabolism by binding to INSULIN-LIKE PEPTIDE 3 (INSL3). However, there have been no reports on RLN function in osteoblast differentiation and mineralization or on the functionally dominant receptors for RLN in osteoblasts. We previously described Rxfp1 and 2 expression patterns in developing mouse oral components, including the maxillary and mandibular bones, Meckel's cartilage, tongue, and tooth primordia. We hypothesized that Rln/Rxfp signaling is a key mediator of skeletal development and metabolism. Here, we present the gene expression patterns of Rxfp1 and 2 in developing mouse calvarial frontal bones as determined by in situ hybridization. In addition, RLN enhanced osteoblastic differentiation and caused abnormal mineralization and extracellular matrix metabolism through Rxfp2, which was predominant over Rxfp1 in MC3T3-E1 mouse calvarial osteoblasts. Our data suggest a novel role for Rln in craniofacial skeletal development and metabolism through Rxfp2.
authors.affiliation: Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Division of Maxillofacial/Neck Reconstruction, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan. Electronic address: caro.duarte1@gmail.com.
authors.forename: Carolina
authors.initials: C
authors.lastname: Duarte
authors.affiliation: Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Division of Maxillofacial/Neck Reconstruction, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan; Hard Tissue Genome Research Center, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510 Japan. Electronic address: yukiho-kobayashi.mort@tmd.ac.jp.
authors.forename: Yukiho
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Division of Maxillofacial/Neck Reconstruction, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan. Electronic address: t-kawamoto.mort@tmd.ac.jp.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kawamoto
authors.affiliation: Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Division of Maxillofacial/Neck Reconstruction, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan; Hard Tissue Genome Research Center, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510 Japan. Electronic address: k-moriyama.mort@tmd.ac.jp.
authors.forename: Keiji
authors.initials: K
authors.lastname: Moriyama
mesh_terms: D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002113:Calcification, Physiologic; D002454:Cell Differentiation / Q000502:physiology*; D051379:Mice; D010766:Phosphorylation; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D012065:Relaxin / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C555886:RXFP2 protein, mouse; D043562:Receptors, G-Protein-Coupled; D012065:Relaxin; D000469:Alkaline Phosphatase
keywords: Collagen; MMP; Osteoblast; RELAXIN; Rxfp2