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AIM The aim of the present study was to determine and compare the expression profile of periostin (POSTN), sclerostin (SOST), receptor activator nuclear factor-κB (RANK), and RANK ligand (RANKL) genes in gingival tissue samples collected from healthy gingiva (control) and severe chronic periodontitis sites. METHODS Fifty systemically-healthy individuals was enrolled in the present case-control study. Gingival tissue samples were obtained from healthy gingiva (N = 25) and sites with severe chronic periodontitis (N = 25). Total RNA was isolated from all the tissues. cDNA conversion was then performed using a reverse transcription polymerase chain reaction (PCR) program. Real-time PCR and SYBR green method were used to determine the expression levels of SOST, POSTN, RANK, and RANKL genes. RESULTS An elevated expression (3.5-4-fold) of SOST, RANK, and RANKL genes, with a concomitant reduced expression of the POSTN gene, was identified in severe chronic periodontitis. The intergroup difference between the mean delta cyclic threshold values showed statistical significance at P<.001. CONCLUSIONS The expression profile of SOST, RANK, RANKL, and POSTN genes observed in gingival tissue samples from sites with severe chronic periodontitis and healthy gingiva suggests that the differential level of the gene expression could serve as an indicator of periodontitis progression/severity.