{"title":"EPLINβ Is Involved in the Assembly of Cadherin-catenin Complexes in Osteoblasts and Affects Bone Formation.","authors":"Shihoko Miyazaki, Taro Funamoto, Tomohisa Sekimoto, Syuji Kurogi, Tomomi Ohta, Takuya Nagai, Takuya Tajima, Mai Imasaka, Kumiko Yoshinobu, Kimi Araki, Masatake Araki, Narantsog Choijookhuu, Yoshitaka Hishikawa, Etsuo Chosa","doi":"10.1267/ahc.22-00027","DOIUrl":null,"url":null,"abstract":"<p><p>Epithelial protein lost in neoplasm (EPLIN) is an actin-associated cytoskeletal protein that plays an important role in epithelial cell adhesion. EPLIN has two isoforms: EPLINα and EPLINβ. In this study, we investigated the role of EPLINβ in osteoblasts using EPLINβ-deficient (<i>EPLINβ<sup>GT/GT</sup></i> ) mice. The skeletal phenotype of <i>EPLINβ<sup>GT/GT</sup></i> mice is indistinguishable from the wildtype (WT), but bone properties and strength were significantly decreased compared with WT littermates. Histomorphological analysis revealed altered organization of bone spicules and osteoblast cell arrangement, and decreased alkaline phosphatase activity in <i>EPLINβ<sup>GT/GT</sup></i> mouse bones. Transmission electron microscopy revealed wider intercellular spaces between osteoblasts in <i>EPLINβ<sup>GT/GT</sup></i> mice, suggesting aberrant cell adhesion. In <i>EPLINβ<sup>GT/GT</sup></i> osteoblasts, α- and β-catenins and F-actin were observed at the cell membrane, but OB-cadherin was localized at the perinuclear region, indicating that cadherin-catenin complexes were not formed. EPLINβ knockdown in MC3T3-e1 osteoblast cells showed similar results as in calvaria cell cultures. Bone formation markers, such as <i>RUNX2</i>, <i>Osterix</i>, <i>ALP</i>, and <i>Col1a1</i> mRNA were reduced in EPLINβ knockdown cells, suggesting an important role for EPLINβ in osteoblast formation. In conclusion, we propose that EPLINβ is involved in the assembly of cadherin-catenin complexes in osteoblasts and affects bone formation.</p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"55 3","pages":"99-110"},"PeriodicalIF":1.6000,"publicationDate":"2022-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e0/ca/ahc_055-99.PMC9253499.pdf","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Histochemica Et Cytochemica","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1267/ahc.22-00027","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/6/25 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 2
Abstract
Epithelial protein lost in neoplasm (EPLIN) is an actin-associated cytoskeletal protein that plays an important role in epithelial cell adhesion. EPLIN has two isoforms: EPLINα and EPLINβ. In this study, we investigated the role of EPLINβ in osteoblasts using EPLINβ-deficient (EPLINβGT/GT ) mice. The skeletal phenotype of EPLINβGT/GT mice is indistinguishable from the wildtype (WT), but bone properties and strength were significantly decreased compared with WT littermates. Histomorphological analysis revealed altered organization of bone spicules and osteoblast cell arrangement, and decreased alkaline phosphatase activity in EPLINβGT/GT mouse bones. Transmission electron microscopy revealed wider intercellular spaces between osteoblasts in EPLINβGT/GT mice, suggesting aberrant cell adhesion. In EPLINβGT/GT osteoblasts, α- and β-catenins and F-actin were observed at the cell membrane, but OB-cadherin was localized at the perinuclear region, indicating that cadherin-catenin complexes were not formed. EPLINβ knockdown in MC3T3-e1 osteoblast cells showed similar results as in calvaria cell cultures. Bone formation markers, such as RUNX2, Osterix, ALP, and Col1a1 mRNA were reduced in EPLINβ knockdown cells, suggesting an important role for EPLINβ in osteoblast formation. In conclusion, we propose that EPLINβ is involved in the assembly of cadherin-catenin complexes in osteoblasts and affects bone formation.
期刊介绍：
Acta Histochemica et Cytochemica is the official online journal of the Japan Society of Histochemistry and Cytochemistry. It is intended primarily for rapid publication of concise, original articles in the fields of histochemistry and cytochemistry. Manuscripts oriented towards methodological subjects that contain significant technical advances in these fields are also welcome. Manuscripts in English are accepted from investigators in any country, whether or not they are members of the Japan Society of Histochemistry and Cytochemistry. Manuscripts should be original work that has not been previously published and is not being considered for publication elsewhere, with the exception of abstracts. Manuscripts with essentially the same content as a paper that has been published or accepted, or is under consideration for publication, will not be considered. All submitted papers will be peer-reviewed by at least two referees selected by an appropriate Associate Editor. Acceptance is based on scientific significance, originality, and clarity. When required, a revised manuscript should be submitted within 3 months, otherwise it will be considered to be a new submission. The Editor-in-Chief will make all final decisions regarding acceptance.
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