Pro-inflammatory cytokines influence proteoglycan expression during alveolar bone formation

Periodontal disease is one of the most prevalent diseases associated with bone loss. Proinflammatory cytokines produced by host cells, in particular interleukin 1-beta (IL-1Β) and tumor necrosis factor-alpha (TNF-α), are key mediators in periodontal tissue destruction. Previous studies have demonstrated roles for decorin (DCN) and biglycan (BGN) proteoglycans in the formation, remodelling and maintenance of mineralised connective tissues (Waddington et al, 2003, Eur. Cells Mats, 6:12-21). The relationship between specific proinflammatory cytokines associated with periodontal tissue destruction may influence the expression of DCN and BGN and the roles they play in mineralised tissue remodelling and repair. Objectives: To investigate the influence of IL-1Β and TNF-α on the expression of DCN and BGN by alveolar bone derived osteoblast-like cells. Methods: Bone cell cultures were established from rat alveolar bone explants, cultured in the presence or absence of 10ng/ml rat recombinant IL-1Β or TNF-α (Sigma) and their effect on cell growth, alkaline phosphatase activity and mineral phosphate deposition examined. During temporal periods associated with active cell growth, production of an extracellular matrix and mineralisation, alveolar bone cell cultures were also examined for the mRNA and protein expression of DCN and BGN. Results: In the presence of both IL-1Β and TNF-α significantly inhibited (p<0.05) alkaline phosphatase as well as the deposition of a mineralised matrix but had no effect on cell growth. IL-1Β and TNF-α inhibited the expression of BGN during phases associated with mineral phosphate deposition (p<0.05). TNF-α also inhibited decorin expression during this time, although IL-1Β enhanced the expression of DCN. Conclusion: Both IL-1Β and TNF-α have the capability to affect the expression of DCN and BGN, which is in turn, may subsequently contribute to the inhibited osteoblastic phenotype development of the alveolar bone cells as well as the tissues attempt at repair.