[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-431095-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-431095-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","inflammatory-bone-loss-and-signaling-pathways-in-periodontitis-mechanistic-insights-and-emerging-therapeutic-strategies-review-article","Inflammatory bone loss and signaling pathways in periodontitis: mechanistic insights and emerging therapeutic strategies - Review article","","Bone resorption supports lifelong skeletal remodeling, yet dysregulation drives diseases including periodontitis, a common chronic inflammatory condition caused by dysbiotic biofilms. The review explains how periodontal bone loss progresses through osteoclast differentiation and activation, emphasizing molecular transcriptional regulators such as NFATc1, c-Fos, and c-Src. It details key signaling pathways (MAPK, JAK/STAT, NF-κB, PI3K/Akt) that coordinate inflammatory responses and osteoclast activity, then surveys hallmark features and current/emerging therapies targeting these mechanisms.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/inflammatory-bone-loss-and-signaling-pathways-in-periodontitis-mechanistic-insights-and-emerging-therapeutic-strategies-review-article/431095/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/inflammatory-bone-loss-and-signaling-pathways-in-periodontitis-mechanistic-insights-and-emerging-therapeutic-strategies-review-article/431095.png","ImageObject",300,407,{"name":42,"@type":43},"Taylor Morgan","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-29",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",11,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What drives inflammatory bone loss in periodontitis according to the review?","Question",{"text":63,"@type":64},"Periodontitis is linked to dysbiotic biofilms that disrupt the oral microbiome, leading to progressive destruction of the periodontium and ultimately tooth loss. The review emphasizes osteoclast differentiation and activation as core mechanisms of bone resorption.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which molecular regulators and signaling pathways are highlighted?",{"text":68,"@type":64},"Key transcriptional regulators include NFATc1, c-Fos, and c-Src. Major pathways discussed are MAPK, JAK/STAT, NF-κB, and PI3K/Akt, which regulate inflammation and osteoclast activity.",{"name":70,"@type":61,"acceptedAnswer":71},"What therapeutic directions does the review emphasize?",{"text":72,"@type":64},"Therapeutic strategies focus on targeting molecular pathways involved in periodontitis. The review highlights small molecules, biologics, and natural compounds that may modulate key signaling routes, while noting that clinical translation remains challenging.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},431095,1790763733,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146,"preview_page_count":4},1099523885336,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","[Bone Research](Bone Research www.nature.com/boneres)[ www.nature.com/boneres](Bone Research www.nature.com/boneres)  \nREVIEW ARTICLE  \nOPEN  \nInflammatory bone loss and signaling pathways in periodontitis: mechanistic insights and emerging therapeutic strategies  \nRafael Scaf de Molon 1 ✉ , Rolando Vernal2, Gabriela Ezequiel Oliveira 1, Joao Paulo Steffens 3, Edilson Ervolino4, Leticia Helena Theodoro1, Jeroen J. J. P. van den Beucken 5 and Sotirios Tetradis6  \n\n|  | Bone resorption is a vital physiological process that enables skeletal remodeling, maintenance, and adaptation to mechanical forces throughout life. While tightly regulated under the physiological state, its dysregulation contributes to pathological conditions such as osteoporosis, rheumatoid arthritis, and periodontitis. Periodontitis is a highly prevalent chronic inflammatory disease driven by dysbiotic biofilms that disrupt the oral microbiome, leading to the progressive breakdown of the periodontal ligament, cementum, and alveolar bone and ultimately resulting in tooth loss. This review outlines the molecular and cellular mechanisms underlying periodontitis, focusing on osteoclastogenesis, the differentiation and activation of osteoclasts, the primary mediators of bone resorption. Key transcriptional regulators, including NFATc1, c-Fos, and c-Src are discussed alongside major signaling pathways such as Mitogen Activated Protein Kinase (MAPK), Janus Tyrosine Kinase/Signal Transducer and Activator of Transcription (JAK/STAT), Nuclear Factor Kappa B (NF-κB), and Phosphoinositide 3-kinase (PI3K)/Akt, to elucidate their roles in the initiation and progression of periodontal bone loss. These pathways orchestrate the inflammatory response and osteoclast activity, underscoring their relevance in periodontitis and other osteolytic conditions. Hallmark features of periodontitis, including chronic inflammation, immune dysregulation, and tissue destruction are highlighted, with emphasis on current and emerging therapeutic strategies targeting these molecular pathways. Special attention is given to small molecules, biologics, and natural compounds that have the potential to modulate key signaling pathways. Although advances in understanding these mechanisms have identified promising therapeutic targets, translation into effective clinical interventions remains challenging. Continued research into regulating boneresorptive signaling pathways is essential for developing more effective treatments for periodontitis and related inflammatory bone |  |\n| --- | --- | --- |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| diseases. |  |  |\n|  | Bone Research (2026)14:1 ; [https://doi.org/10.1038/s41413-025-00478-1](https://doi.org/10.1038/s41413-025-00478-1) |  |\n|  |  |  |\n\nINTRODUCTION  \nBone resorption is a fundamental physiological process that enables remodeling, maintaining, and continuously renewing the skeleton throughout life. However, dysregulation of this process can lead to several pathological conditions, including periodontitis.1 Periodontitis, a non-communicable chronic and inflammatory disease linked to a dysbiotic biofilm, affects the teethsupporting tissues due to progressive destruction of the periodontal ligament, cement, and alveolar bone.2,3 (Fig. 1) .  \nThis pathological process is intricately linked to the host immune response, which plays a central role in the disease initiation, progression, and exacerbation.4–7 Severe periodontitis affects more than 700 million individuals globally, accounting for approximately 11% of the world’s population.8 In developed nations, prevalence rates remain high, ranging from 7 . 2% to 9 .8% .9 In the United States alone, an estimated 64.7 million adults (46% of the population) are affected by periodontitis, with 8.9% experiencing severe cases.10 In Brazil, the severe forms of  \nperiodontitis account for a","cbCaicKoyLge54Pp","https://ap.wps.com/l/cbCaicKoyLge54Pp","pdf",4461130,27,"English","# Introduction\n## Bone resorption and periodontitis overview\n## Immune response and epidemiological impact\n## Links to systemic chronic diseases","[{\"question\":\"What drives inflammatory bone loss in periodontitis according to the review?\",\"answer\":\"Periodontitis is linked to dysbiotic biofilms that disrupt the oral microbiome, leading to progressive destruction of the periodontium and ultimately tooth loss. The review emphasizes osteoclast differentiation and activation as core mechanisms of bone resorption.\"},{\"question\":\"Which molecular regulators and signaling pathways are highlighted?\",\"answer\":\"Key transcriptional regulators include NFATc1, c-Fos, and c-Src. Major pathways discussed are MAPK, JAK/STAT, NF-κB, and PI3K/Akt, which regulate inflammation and osteoclast activity.\"},{\"question\":\"What therapeutic directions does the review emphasize?\",\"answer\":\"Therapeutic strategies focus on targeting molecular pathways involved in periodontitis. The review highlights small molecules, biologics, and natural compounds that may modulate key signaling routes, while noting that clinical translation remains challenging.\"}]","Inflammatory bone loss and signaling pathways in periodontitis: mechanistic insights and emerging therapeutic strategies - Review article | PDF",1790654496,68]