Ka-Young Ryu, N. K. Pokhrel, Hye-Jin Jung, Hyo Jeong Kim, Jiwon Seok, Tae-Young Kim, Hyung Joon Kim, Ji Hye Lee, Jae-Young Kim, Yong-Gun Kim, Youngkyun Lee
{"title":"Mer 酪氨酸激酶调节骨代谢,缺乏它可部分改善牙周炎和卵巢切除术诱发的小鼠骨质流失","authors":"Ka-Young Ryu, N. K. Pokhrel, Hye-Jin Jung, Hyo Jeong Kim, Jiwon Seok, Tae-Young Kim, Hyung Joon Kim, Ji Hye Lee, Jae-Young Kim, Yong-Gun Kim, Youngkyun Lee","doi":"10.1093/jbmrpl/ziad014","DOIUrl":null,"url":null,"abstract":"\n Bone homeostasis is maintained by tightly coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts. In the present report, the role of Mer tyrosine kinase (MerTK) in bone metabolism was investigated. The expression of MerTK decreased upon BMP2 stimulation of osteoblast precursors. The femurs of Mertk-deficient mice showed significantly increased bone volume with concomitant increase of bone formation and reduction in bone resorption. These bone phenotypes were attributed to the increased osteoblast differentiation and mineralization accounted by the enhanced β-Catenin and Smad signaling in the absence of MerTK in osteoblast precursors. Although the Mertk-deficient bone marrow macrophages were predisposed to enhanced osteoclast differentiation via augmented Ca2+-NFATc1 signaling, the dramatic increase of Tnfsf11b/Tnfsf11 (Opg/Rankl) ratio in Mertk knockout bones and osteoblast precursors corroborated the reduction of osteoclastogenesis in Mertk deficiency. In ligature-induced periodontitis and ovariectomy models, the bone resorption was significantly attenuated in Mertk-deficient mice compared with wild type control. Taken together, these data indicate novel role of MerTK in bone metabolism and suggest a potential strategy targeting MerTK in treating bone-lytic diseases including periodontitis and osteoporosis.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mer tyrosine kinase regulates bone metabolism, and its deficiency partially ameliorates periodontitis- and ovariectomy-induced bone loss in mice\",\"authors\":\"Ka-Young Ryu, N. K. Pokhrel, Hye-Jin Jung, Hyo Jeong Kim, Jiwon Seok, Tae-Young Kim, Hyung Joon Kim, Ji Hye Lee, Jae-Young Kim, Yong-Gun Kim, Youngkyun Lee\",\"doi\":\"10.1093/jbmrpl/ziad014\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"\\n Bone homeostasis is maintained by tightly coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts. In the present report, the role of Mer tyrosine kinase (MerTK) in bone metabolism was investigated. The expression of MerTK decreased upon BMP2 stimulation of osteoblast precursors. The femurs of Mertk-deficient mice showed significantly increased bone volume with concomitant increase of bone formation and reduction in bone resorption. These bone phenotypes were attributed to the increased osteoblast differentiation and mineralization accounted by the enhanced β-Catenin and Smad signaling in the absence of MerTK in osteoblast precursors. Although the Mertk-deficient bone marrow macrophages were predisposed to enhanced osteoclast differentiation via augmented Ca2+-NFATc1 signaling, the dramatic increase of Tnfsf11b/Tnfsf11 (Opg/Rankl) ratio in Mertk knockout bones and osteoblast precursors corroborated the reduction of osteoclastogenesis in Mertk deficiency. In ligature-induced periodontitis and ovariectomy models, the bone resorption was significantly attenuated in Mertk-deficient mice compared with wild type control. Taken together, these data indicate novel role of MerTK in bone metabolism and suggest a potential strategy targeting MerTK in treating bone-lytic diseases including periodontitis and osteoporosis.\",\"PeriodicalId\":14611,\"journal\":{\"name\":\"JBMR Plus\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-01-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JBMR Plus\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/jbmrpl/ziad014\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JBMR Plus","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/jbmrpl/ziad014","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Mer tyrosine kinase regulates bone metabolism, and its deficiency partially ameliorates periodontitis- and ovariectomy-induced bone loss in mice
Bone homeostasis is maintained by tightly coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts. In the present report, the role of Mer tyrosine kinase (MerTK) in bone metabolism was investigated. The expression of MerTK decreased upon BMP2 stimulation of osteoblast precursors. The femurs of Mertk-deficient mice showed significantly increased bone volume with concomitant increase of bone formation and reduction in bone resorption. These bone phenotypes were attributed to the increased osteoblast differentiation and mineralization accounted by the enhanced β-Catenin and Smad signaling in the absence of MerTK in osteoblast precursors. Although the Mertk-deficient bone marrow macrophages were predisposed to enhanced osteoclast differentiation via augmented Ca2+-NFATc1 signaling, the dramatic increase of Tnfsf11b/Tnfsf11 (Opg/Rankl) ratio in Mertk knockout bones and osteoblast precursors corroborated the reduction of osteoclastogenesis in Mertk deficiency. In ligature-induced periodontitis and ovariectomy models, the bone resorption was significantly attenuated in Mertk-deficient mice compared with wild type control. Taken together, these data indicate novel role of MerTK in bone metabolism and suggest a potential strategy targeting MerTK in treating bone-lytic diseases including periodontitis and osteoporosis.