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Aim Porphyromonas gingivalis ( Pg) may cause an immune-inflammatory response in host cells leading to bone degradation by osteoclasts. We investigated the osteoclast-inducing capacity of periodontal ligament fibroblasts from periodontitis patients and non-periodontitis donors after a challenge with viable Pg. Materials and methods PDLFs from periodontitis patients ( n = 8) and non-periodontitis donors ( n = 7) were incubated for 6 h with or without viable Pg and subsequently co-cultured with osteoclast precursors from peripheral blood mononuclear cells ( PBMCs). The number of multinucleated tartrate-resistant acid phosphatase-positive cells was determined at 21 days. Expression of osteoclastogenesis-associated genes was assessed after infection of PDLFs mono-cultures and in PDLFs- PBMCs co-cultures. Resorption activity was analysed on bone slices. Results Pg induced the expression of osteoclastogenesis-associated genes by PDLFs. After bacterial challenge the formation of osteoclast-like cell was decreased in co-cultures of PBMCs with non-periodontitis PDLFs, but not with PDLFs from periodontitis patients. Conclusion PDLFs from sites free of periodontitis respond to an infection with Pg by tempering formation of osteoclast-like cells, probably promoting clearance of the infection. PDLFs from periodontitis sites are desensitized to a Pg challenge in terms of their osteoclast-inducing capacity. [ABSTRACT FROM AUTHOR]