Effect of Tanshinone Sodium Sulfonate on the Modulation of the Immunoinflammatory Profile and Bone Metabolism in a Mouse Model of Periodontitis

• Grant number: 25/09939-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2025
• End date: July 31, 2026
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Rafael Scaf de Molon
• Grantee: João Pedro Franco Moura
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

Bone resorption is a fundamental physiological process involved in the continuous remodeling, maintenance, and renewal of the skeleton throughout life. This dynamic mechanism enables bone tissue to constantly adapt to mechanical demands while preserving its structural integrity. However, when dysregulated, bone resorption can contribute to the development of several pathological conditions, including osteoporosis, rheumatoid arthritis, and periodontal disease. Periodontitis is a highly prevalent chronic inflammatory condition characterized by dysbiotic bacterial biofilms that disrupt the balance of the oral microbiome. This dysbiosis triggers an exacerbated inflammatory response, leading to the progressive destruction of the tooth-supporting structures, including the periodontal ligament, cementum, and alveolar bone. In this context, therapeutic strategies targeting the inhibition of osteoclast differentiation or activity - the specialized cells responsible for bone resorption - have shown promise in controlling periodontitis-associated bone loss. Among the compounds under investigation, Tanshinones-natural bioactive molecules extracted from Salvia miltiorrhiza (commonly known as Danshen)-stand out for their relevant pharmacological properties, including anti-inflammatory and antiresorptive effects. Tanshinone IIA sulfonate, in particular, has been shown to inhibit the collagenolytic activity of Cathepsin K - an enzyme secreted by osteoclasts that plays a key role in the degradation of the organic matrix of bone - without directly interfering with osteoclast differentiation.Given the therapeutic potential of Tanshinone IIA sulfonate, this study aims to investigate the effects of its local application on immune and inflammatory responses, as well as bone remodeling, in a mouse model of ligature-induced bone loss. Immunofluorescence analysis will be used to assess immunoinflammatory profiles through markers such as anti-CD80, anti-CD206, anti-F4/80, anti-CD4, anti-CD8, and anti-CD45. In addition, markers related to bone metabolism, including OPG, RANKL, and Cathepsin K, as well as transcription factors associated with osteoclastogenesis and osteoblast differentiation (RUNX-2, NFATc1, and NF-¿B), will be quantified by immunohistochemistry.