Myeloid-Derived Grancalcin Promotes Periodontal Inflammation and Pathological Bone Remodeling in Periodontitis

Area of Science:

• Oral biology
• Immunology
• Biochemistry

Background:

• Periodontitis is a prevalent chronic oral inflammatory disease causing significant inflammation and alveolar bone loss.
• The precise molecular mechanisms underlying periodontitis pathogenesis remain incompletely elucidated.
• Myeloid-derived cells and their secreted factors play a role in oral inflammatory conditions.

Purpose of the Study:

• To identify novel molecular regulators involved in periodontitis.
• To investigate the role of grancalcin (GCA) in the pathogenesis of periodontitis.
• To explore GCA as a potential therapeutic target for periodontitis.

Main Methods:

• Quantification of grancalcin (GCA) expression in human and mouse periodontitis models.
• Genetic ablation studies (global knockout and myeloid-specific conditional deletion) of GCA.
• Investigation of GCA's molecular interactions with CD44 and MYH9 in human gingival fibroblasts.
• Analysis of NF-κB pathway activation and p65 nuclear translocation.
• Evaluation of a GCA-neutralizing antibody and a thermosensitive hydrogel delivery system in periodontitis models.

Main Results:

• Grancalcin (GCA) was significantly enriched in the gingival tissues of periodontitis patients and mouse models.
• Genetic deletion of GCA substantially reduced periodontal inflammation and pathological bone remodeling.
• GCA was found to interact with CD44, activating MYH9 and subsequently the NF-κB pathway, leading to inflammation and bone resorption.
• A GCA-neutralizing antibody and a localized hydrogel delivery system effectively alleviated periodontitis.

Conclusions:

• Grancalcin (GCA) is a critical, previously unrecognized regulator of periodontitis.
• GCA promotes periodontal inflammation and bone loss through the CD44-MYH9-NF-κB axis.
• GCA represents a promising molecular marker and therapeutic target for periodontitis treatment.