start-ver=1.4 cd-journal=joma no-vol=17 cd-vols= no-issue=9 article-no= start-page=1559 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250503 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Impacts of Dental Follicle Cells and Periodontal Ligament Cells on the Bone Invasion of Well-Differentiated Oral Squamous Cell Carcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=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-kappa B 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. en-copyright= kn-copyright= en-aut-name=ChangAnqi en-aut-sei=Chang en-aut-mei=Anqi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakabatakeKiyofumi en-aut-sei=Takabatake en-aut-mei=Kiyofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=PiaoTianyan en-aut-sei=Piao en-aut-mei=Tianyan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ArashimaTakuma en-aut-sei=Arashima en-aut-mei=Takuma kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawaiHotaka en-aut-sei=Kawai en-aut-mei=Hotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EainHtoo Shwe en-aut-sei=Eain en-aut-mei=Htoo Shwe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SoeYamin en-aut-sei=Soe en-aut-mei=Yamin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MinZin Zin en-aut-sei=Min en-aut-mei=Zin Zin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakanoKeisuke en-aut-sei=Nakano en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NagatsukaHitoshi en-aut-sei=Nagatsuka en-aut-mei=Hitoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=2 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=3 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=4 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=5 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=6 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=7 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=8 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=9 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= affil-num=10 en-affil=Department of Oral Pathology and Medicine, Okayama University kn-affil= en-keyword=oral squamous cell carcinoma kn-keyword=oral squamous cell carcinoma en-keyword=dental follicle cells kn-keyword=dental follicle cells en-keyword=periodontal ligament cells kn-keyword=periodontal ligament cells en-keyword=bone invasion kn-keyword=bone invasion en-keyword=receptor activator of NF-kappa B ligand kn-keyword=receptor activator of NF-kappa B ligand en-keyword=parathyroid hormone-related peptide kn-keyword=parathyroid hormone-related peptide END