# Impacts of Dental Follicle Cells and Periodontal Ligament Cells on the Bone Invasion of Well-Differentiated Oral Squamous Cell Carcinoma

## TL;DR

This study shows how dental follicle cells and periodontal ligament cells affect bone invasion in oral cancer, suggesting new treatment strategies.

## Contribution

The study reveals opposing roles of dental follicle and periodontal ligament cells in promoting or suppressing oral cancer bone invasion.

## Key findings

- Dental follicle cells enhance bone destruction by stimulating osteoclasts.
- Periodontal ligament cells suppress bone resorption by reducing RANKL expression.
- Stromal cell interactions influence oral cancer progression and could be targeted therapeutically.

## Abstract

Oral squamous cell carcinoma is a common head and neck cancer that often spreads into the jawbone, leading to severe complications. Understanding the factors that promote or inhibit this process is essential for improving treatment strategies. In this study, we examined two types of dental cells—dental follicle cells and periodontal ligament cells—to explore their effects on cancer-associated bone invasion. Our results show that dental follicle cells enhance bone destruction by stimulating bone-resorbing cells (osteoclasts), whereas periodontal ligament cells suppress this process, potentially protecting against tumor invasion. These findings reveal how stromal cells influence cancer progression and suggest that targeting these interactions could lead to new therapeutic approaches for bone-invasive oral cancer.

Background: Oral squamous cell carcinoma (OSCC) frequently invades the jawbone, leading to diagnostic and therapeutic challenges. While tumor–bone interactions have been studied, the specific roles of dental follicle cells (DFCs) and periodontal ligament cells (PDLCs) in OSCC-associated bone resorption remain unclear. This study aimed to compare the effects of DFCs and PDLCs on OSCC-induced bone invasion and elucidate the underlying mechanisms. Methods: Primary human DFCs and PDLCs were isolated from extracted third molars and characterized by Giemsa and immunofluorescence staining. An in vitro co-culture system and an in vivo xenograft mouse model were established using the HSC-2 OSCC cell line. Tumor invasion and osteoclast activation were assessed by hematoxylin and eosin (HE) and tartrate-resistant acid phosphatase (TRAP) staining. Immunohistochemical analysis was performed to evaluate the expression of receptor activator of NF-κB ligand (RANKL) and parathyroid hormone-related peptide (PTHrP). Results: DFCs significantly enhanced OSCC-induced bone resorption by promoting osteoclastogenesis and upregulating RANKL and PTHrP expression. In contrast, PDLCs suppressed RANKL expression and partially modulated PTHrP levels, thereby reducing osteoclast activity. Conclusions: DFCs and PDLCs exert opposite regulatory effects on OSCC-associated bone destruction. These findings underscore the importance of stromal heterogeneity and highlight the therapeutic potential of targeting specific stromal–tumor interactions to mitigate bone-invasive OSCC.