[P-058] 薬剤性歯肉増殖症におけるSPOCK-1の役割
The role of SPOCK-1 in Drug induced gingival overgrowth（DIGO）
研修コード：2299
Keywords:薬剤性歯肉増殖症、SPOCK-1
Introduction: Gingival overgrowth is a side effect associated with phenytoin（PHE）, cyclosporin A（CsA）and nifedipine（NFD）. Various studies have suggested an interaction between those drugs and gingival fibroblasts which will ultimately lead to either increase in matrix synthesis or in impaired intracellular matrix digestion by lysosomal cysteine proteases as cathepsins. However, the mechanism by which those drugs cause DIGO is not fully understood. We previously suggested complete loss of cathepsin-L（CtsL）function promoted gingival overgrowth. SPOCK-1, belonging to proteoglycan family, is a specific inhibitor of CtsL. The aim of this research is to investigate the role of SPOCK-1 in DIGO.
Materials & methods: Human gingival fibroblasts were collected from patients who underwent flap operations at Kyushu University Hospital. The cells were stimulated with PHE, CsA or NFD. The mRNA levels of Spock-1, MMP-2 and TIMP1 were examined by quantitative real time PCR.
Results: Results indicated that PHE, CsA and NFD promoted the expression of SPOCK-1. MMP2 expression was significantly decreased in every samples. TIMP-1 expression was not influenced by CsA or NFD, but decreased slightly by PHE.
Conclusions: SPOCK-1 upregulation was common among the three drugs used, which may indicate the important role of SPOCK-1 in the pathophysiology of DIGO. Since SPOCK-1 is a family of proteoglycan, the result supports the hypothesis that causative drugs upregulate ECM production and suppress degradation of excess matrix proteins.
Materials & methods: Human gingival fibroblasts were collected from patients who underwent flap operations at Kyushu University Hospital. The cells were stimulated with PHE, CsA or NFD. The mRNA levels of Spock-1, MMP-2 and TIMP1 were examined by quantitative real time PCR.
Results: Results indicated that PHE, CsA and NFD promoted the expression of SPOCK-1. MMP2 expression was significantly decreased in every samples. TIMP-1 expression was not influenced by CsA or NFD, but decreased slightly by PHE.
Conclusions: SPOCK-1 upregulation was common among the three drugs used, which may indicate the important role of SPOCK-1 in the pathophysiology of DIGO. Since SPOCK-1 is a family of proteoglycan, the result supports the hypothesis that causative drugs upregulate ECM production and suppress degradation of excess matrix proteins.