{"title":"BMP-2功能多肽通过双调节骨形成和吸收以及巨噬细胞极化来缓解骨溶解。","authors":"Jiaqian Wang, Yuan Xue, Yi Wang, Chang Liu, Sihan Hu, Huan Zhao, Qiaoli Gu, Huilin Yang, Lixin Huang, Xichao Zhou, Qin Shi","doi":"10.1038/s41536-023-00279-2","DOIUrl":null,"url":null,"abstract":"<p><p>Osteolysis caused by wear debris around the prosthesis is the main reason for aseptic loosening. Extending prosthetic service life is still challenging. In this study, we first synthesized a bone morphogenetic protein-2 (BMP-2) functional polypeptide (BMP2pp), and evaluated the effects of BMP2pp on macrophage polarization and impaired osteogenesis caused by titanium (Ti) particles in vitro. Then, we delineated the impact of BMP2pp on bone formation and resorption in a mouse calvarial bone osteolysis model induced by Ti particles. The results showed that BMP2pp not only alleviated the Ti-induced inhibition of osteoblastic differentiation in human placenta-derived mesenchymal stem cells (hPMSCs) but also prevented Ti-induced M1 macrophage polarization and promoted M2 macrophage differentiation in mice. Conditioned medium from BMP2pp-activated macrophages increased the osteogenesis of hPMSCs. The western blot results indicated a significant decrease in the expression of NF-κB inducing kinase (NIK) and phospho-NF-κB p65 in bone marrow-derived macrophages treated with BMP2pp. Furthermore, we clarified the protective effect of BMP2pp on bone formation and the reduction in bone resorption coupled with the immunomodulatory properties of calvarial osteolysis in mice. In summary, BMP2pp ameliorated the Ti-mediated impairment in osteogenic potential of hPMSCs, suppressed the M1 polarization of macrophages by inhibiting the activation of the NF-κB signaling pathway, and ameliorated Ti-induced bone osteolysis. Our research suggests that BMP2pp may be a potential option for treating prosthetic loosening induced by wear debris from prostheses.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":null,"pages":null},"PeriodicalIF":6.4000,"publicationDate":"2023-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9911742/pdf/","citationCount":"4","resultStr":"{\"title\":\"BMP-2 functional polypeptides relieve osteolysis via bi-regulating bone formation and resorption coupled with macrophage polarization.\",\"authors\":\"Jiaqian Wang, Yuan Xue, Yi Wang, Chang Liu, Sihan Hu, Huan Zhao, Qiaoli Gu, Huilin Yang, Lixin Huang, Xichao Zhou, Qin Shi\",\"doi\":\"10.1038/s41536-023-00279-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Osteolysis caused by wear debris around the prosthesis is the main reason for aseptic loosening. Extending prosthetic service life is still challenging. In this study, we first synthesized a bone morphogenetic protein-2 (BMP-2) functional polypeptide (BMP2pp), and evaluated the effects of BMP2pp on macrophage polarization and impaired osteogenesis caused by titanium (Ti) particles in vitro. Then, we delineated the impact of BMP2pp on bone formation and resorption in a mouse calvarial bone osteolysis model induced by Ti particles. The results showed that BMP2pp not only alleviated the Ti-induced inhibition of osteoblastic differentiation in human placenta-derived mesenchymal stem cells (hPMSCs) but also prevented Ti-induced M1 macrophage polarization and promoted M2 macrophage differentiation in mice. Conditioned medium from BMP2pp-activated macrophages increased the osteogenesis of hPMSCs. The western blot results indicated a significant decrease in the expression of NF-κB inducing kinase (NIK) and phospho-NF-κB p65 in bone marrow-derived macrophages treated with BMP2pp. Furthermore, we clarified the protective effect of BMP2pp on bone formation and the reduction in bone resorption coupled with the immunomodulatory properties of calvarial osteolysis in mice. In summary, BMP2pp ameliorated the Ti-mediated impairment in osteogenic potential of hPMSCs, suppressed the M1 polarization of macrophages by inhibiting the activation of the NF-κB signaling pathway, and ameliorated Ti-induced bone osteolysis. Our research suggests that BMP2pp may be a potential option for treating prosthetic loosening induced by wear debris from prostheses.</p>\",\"PeriodicalId\":54236,\"journal\":{\"name\":\"npj Regenerative Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.4000,\"publicationDate\":\"2023-02-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9911742/pdf/\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"npj Regenerative Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41536-023-00279-2\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"npj Regenerative Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41536-023-00279-2","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
BMP-2 functional polypeptides relieve osteolysis via bi-regulating bone formation and resorption coupled with macrophage polarization.
Osteolysis caused by wear debris around the prosthesis is the main reason for aseptic loosening. Extending prosthetic service life is still challenging. In this study, we first synthesized a bone morphogenetic protein-2 (BMP-2) functional polypeptide (BMP2pp), and evaluated the effects of BMP2pp on macrophage polarization and impaired osteogenesis caused by titanium (Ti) particles in vitro. Then, we delineated the impact of BMP2pp on bone formation and resorption in a mouse calvarial bone osteolysis model induced by Ti particles. The results showed that BMP2pp not only alleviated the Ti-induced inhibition of osteoblastic differentiation in human placenta-derived mesenchymal stem cells (hPMSCs) but also prevented Ti-induced M1 macrophage polarization and promoted M2 macrophage differentiation in mice. Conditioned medium from BMP2pp-activated macrophages increased the osteogenesis of hPMSCs. The western blot results indicated a significant decrease in the expression of NF-κB inducing kinase (NIK) and phospho-NF-κB p65 in bone marrow-derived macrophages treated with BMP2pp. Furthermore, we clarified the protective effect of BMP2pp on bone formation and the reduction in bone resorption coupled with the immunomodulatory properties of calvarial osteolysis in mice. In summary, BMP2pp ameliorated the Ti-mediated impairment in osteogenic potential of hPMSCs, suppressed the M1 polarization of macrophages by inhibiting the activation of the NF-κB signaling pathway, and ameliorated Ti-induced bone osteolysis. Our research suggests that BMP2pp may be a potential option for treating prosthetic loosening induced by wear debris from prostheses.
期刊介绍:
Regenerative Medicine, an innovative online-only journal, aims to advance research in the field of repairing and regenerating damaged tissues and organs within the human body. As a part of the prestigious Nature Partner Journals series and in partnership with ARMI, this high-quality, open access journal serves as a platform for scientists to explore effective therapies that harness the body's natural regenerative capabilities. With a focus on understanding the fundamental mechanisms of tissue damage and regeneration, npj Regenerative Medicine actively encourages studies that bridge the gap between basic research and clinical tissue repair strategies.