{"title":"Gingival fibroblast suppress the osteogenesis process mediated by bone substitute materials via WNT/β-catenin signaling pathway <i>in vitro</i> and <i>in vivo</i>.","authors":"Guanqi Liu, Jiahui Lin, Xiaoyan Chen, Runheng Liu","doi":"10.3389/fbioe.2025.1521134","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The regeneration of bone tissue is a critical challenge in oral and maxillofacial surgery, with the success of such procedures often depending on the ability to promote osteogenesis while managing the soft tissue environment. The role of gingival fibroblasts in modulating the osteogenic potential of mandible mesenchymal stem cells (MMSCs) mediated by bone substitute materials (BSMs) is not fully understood. This study aimed to investigate the impact of gingival fibroblasts on the osteogenic differentiation of MSCs in the presence of BSMs and to elucidate the underlying mechanisms, focusing on the WNT/β-catenin signaling pathway.</p><p><strong>Methods: </strong>Gingival fibroblasts and BSMs co-culture conditioned medium was used to culture MMSCs, and the expression and activity of alkaline phosphatase (ALP), as well as osteogenic and fibrogenic gene and protein expression, were evaluated. Additionally, the expression of key factors of WNT/β-catenin signaling pathway were investigated. <i>In vivo</i> animal experiments were conducted to assess the effect of gingival fibroblasts on BSM-mediated bone regeneration.</p><p><strong>Results: </strong>Gingival fibroblasts and BSMs co-culture environment did not affect MMSCs proliferation but significantly inhibited ALP expression and activity, as well as osteogenic gene and protein expression, while promoting expression of fibrogenic markers. This suppression was associated with the downregulation of key factors in the WNT/β-catenin signaling pathway. <i>In vivo</i>, increased suppression of bone defect repair was observed with higher amounts of gingival fibroblasts, confirming the <i>in vitro</i> findings.</p><p><strong>Conclusion: </strong>Our study demonstrates that gingival fibroblasts can suppress the osteogenic potential of BSMs by inhibiting the autocrine WNT expression and the activation of the WNT/β-catenin signaling pathway in MMSCs. These findings highlight the importance of considering the cellular microenvironment in tissue engineering and regenerative medicine and suggest potential targets for modulating MMSCs behavior to enhance bone regeneration.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1521134"},"PeriodicalIF":4.8000,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847790/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Bioengineering and Biotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.3389/fbioe.2025.1521134","RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The regeneration of bone tissue is a critical challenge in oral and maxillofacial surgery, with the success of such procedures often depending on the ability to promote osteogenesis while managing the soft tissue environment. The role of gingival fibroblasts in modulating the osteogenic potential of mandible mesenchymal stem cells (MMSCs) mediated by bone substitute materials (BSMs) is not fully understood. This study aimed to investigate the impact of gingival fibroblasts on the osteogenic differentiation of MSCs in the presence of BSMs and to elucidate the underlying mechanisms, focusing on the WNT/β-catenin signaling pathway.
Methods: Gingival fibroblasts and BSMs co-culture conditioned medium was used to culture MMSCs, and the expression and activity of alkaline phosphatase (ALP), as well as osteogenic and fibrogenic gene and protein expression, were evaluated. Additionally, the expression of key factors of WNT/β-catenin signaling pathway were investigated. In vivo animal experiments were conducted to assess the effect of gingival fibroblasts on BSM-mediated bone regeneration.
Results: Gingival fibroblasts and BSMs co-culture environment did not affect MMSCs proliferation but significantly inhibited ALP expression and activity, as well as osteogenic gene and protein expression, while promoting expression of fibrogenic markers. This suppression was associated with the downregulation of key factors in the WNT/β-catenin signaling pathway. In vivo, increased suppression of bone defect repair was observed with higher amounts of gingival fibroblasts, confirming the in vitro findings.
Conclusion: Our study demonstrates that gingival fibroblasts can suppress the osteogenic potential of BSMs by inhibiting the autocrine WNT expression and the activation of the WNT/β-catenin signaling pathway in MMSCs. These findings highlight the importance of considering the cellular microenvironment in tissue engineering and regenerative medicine and suggest potential targets for modulating MMSCs behavior to enhance bone regeneration.
期刊介绍：
The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs.
In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
