Leptin Receptor-Expressing (LepR⁺) Fibroblasts Activated by BMP Signaling Promote Bone Resorption in Developmental...

Area of Science:

• Oral and Maxillofacial Surgery
• Developmental Biology
• Cell Biology

Background:

• Cystic lesions are common in jawbones, with developmental odontogenic cysts often growing large before detection.
• The pathogenesis and progression mechanisms of developmental odontogenic cysts are not fully understood.
• Understanding bone resorption in these cysts is crucial for effective treatment.

Purpose of the Study:

• To elucidate the mechanisms of bone resorption in developmental odontogenic cysts.
• To identify key cellular players and signaling pathways involved in cyst-induced bone erosion.
• To differentiate developmental odontogenic cysts from benign dental follicles.

Main Methods:

• Single-cell RNA sequencing of dentigerous cysts (DCs) and dental follicles.
• Cell-to-cell interaction analysis to identify communication pathways.
• In vitro experiments using mouse bone marrow cells treated with fibroblast culture supernatants.
• Inhibition of bone morphogenetic protein signaling to assess its role.

Main Results:

• Activated plasma cells and leptin receptor-expressing (LepR+) fibroblasts were identified in DCs.
• LepR+ fibroblasts showed strong interactions with plasma cells via bone morphogenetic protein 6 signaling.
• LepR+ fibroblasts expressed high levels of osteoclastogenesis-related genes (CSF1, IL6, IL34).
• LepR+ fibroblast supernatants induced osteoclast formation and bone resorption in vitro.
• Inhibition of bone morphogenetic protein signaling reduced osteoclastogenesis.

Conclusions:

• LepR+ fibroblasts are a key distinguishing feature of developmental odontogenic cysts compared to dental follicles.
• A novel mechanism involving LepR+ fibroblast-mediated osteoclast induction and bone resorption in DCs is confirmed.
• This finding may inform future therapeutic strategies for developmental odontogenic cysts.