osteoprotegerin and Basal-Cell-Nevus-Syndrome

Keratocystic odontogenic tumors (KCOTs) are jaw lesions that can be either sporadic or associated with nevoid basal cell carcinoma syndrome, which typically occurs as multiple, aggressive lesions that can lead to large areas of bone destruction and resorption and cause major impairment and even jaw fracture. To clarify the role of fibroblasts in the aggressivness of syndromic (S-) as compared with non-syndromic (NS-) KCOTs, we assessed fibroblasts derived from 16 S- and NS-KCOTs for differences in cell proliferation, multilineage differentiation potential, alkaline phosphatase activity, and osteoclastogenic potential. S-KCOT fibroblasts had proliferative and osteoclastogenic capacity higher than those from NS-KCOTs, as evidenced by higher numbers of tartrate-resistant acid-phosphatase-positive multinuclear cells, expression of cyclooxygenase 2, and ratio of receptor activator of nuclear factor-kappa B ligand to osteoprotegerin. The osteogenic potential was higher for S- than for NS-KCOT fibroblasts and was associated with lower mRNA expression of runt-related transcription factor 2, collagen type I α1, osteocalcin, and osteopontin as well as reduced alkaline phosphatase activity. These results suggest that the distinct characteristics of fibroblasts in KCOTs are responsible for the greater aggressiveness observed in the syndromic subtype.. AP, alkaline phosphatase; CK, cytokeratin; COL1A1, collagen type I α1; COX-2, cyclooxygenase-2; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL-1α, interleukin 1α; KCOT, keratocystic odontogenic tumor; NBCCS, nevoid basal cell carcinoma syndrome; NS-KCOT, non-syndrome-associated KCOT; OCN, osteocalcin; OPG, osteoprotegerin; OPN, osteopontin; RANKL, receptor activator of nuclear factor-kappa B ligand; Runx2, runt-related transcription factor 2; S-KCOT, syndrome-associated KCOT; TAF, tumor-associated fibroblast; and TRAP, tartrate-resistant acid phosphatase.

Topics: Acid Phosphatase; Alkaline Phosphatase; Basal Cell Nevus Syndrome; Biomarkers; Cell Culture Techniques; Cell Differentiation; Cell Line; Cell Lineage; Cell Nucleus; Cell Proliferation; Collagen Type I; Collagen Type I, alpha 1 Chain; Core Binding Factor Alpha 1 Subunit; Cyclooxygenase 2; Fibroblasts; Humans; Isoenzymes; Jaw Neoplasms; Odontogenic Tumors; Osteoblasts; Osteocalcin; Osteoclasts; Osteogenesis; Osteopontin; Osteoprotegerin; RANK Ligand; Tartrate-Resistant Acid Phosphatase

The aim of this study was to immunohistochemically analyse bone resorption regulators (receptor activator of nuclear factor kappa B ligand [RANKL] and osteoprotegerin [OPG]), angiogenic index, and myofibroblasts in Gorlin syndrome-related odontogenic keratocysts (SOKCs) and non-syndrome odontogenic keratocysts (NSOKCs).. Twenty-two SOKCs, 22 primary NSOKCs, and eight recurrent NSOKCs were evaluated by immunohistochemistry using anti-RANKL and anti-OPG antibodies. The angiogenic index was determined by microvessel count (MVC) using anti-CD34 antibody. Anti-α-smooth muscle actin (α-SMA) antibody was used for the identification of myofibroblasts.. Analysis of the expression of RANKL and OPG in the epithelial lining and fibrous capsule did not reveal significant differences between groups (P>0.05). In the epithelial lining, the RANKL/OPG ratio was RANKL0.05). In the fibrous capsule, the ratio was RANKL=OPG in most primary (81.8%) and recurrent NSOKCs (75.0%) and in most SOKCs (45.5%) (P>0.05). No significant differences in the angiogenic index or number of myofibroblasts were observed between primary NSOKCs, recurrent NSOKCs, and SOKCs (P>0.05).. The present results suggest that differences in the biological behaviour of SOKCs and NSOKCs may not be related to the expression of RANKL and OPG, to the RANKL/OPG ratio, to the angiogenic index, or to the number of myofibroblasts in these lesions.

Topics: Antigens, CD34; Basal Cell Nevus Syndrome; Bone Resorption; Epithelial Cells; Humans; Immunohistochemistry; Myofibroblasts; Neovascularization, Pathologic; Odontogenic Cysts; Osteoprotegerin; RANK Ligand