Low concentration of lipopolysaccharide acts on MC3T3-E1 osteoblasts and induces proliferation via the COX-2-independent NFkappaB pathway.

The translocations of lipopolysaccharide (LPS) from the gut and its effects on bone healing are usually of clinical interest during bone fracture. As already widely studied, Cyclooxygenase-2 (COX-2) is a key enzyme for prostaglandin E2 (PGE(2)) production, which induces the nuclear factor kappa B (NFkappaB) activation and is beneficial to fracture healing. In order to know their roles in skeletal regeneration, mouse MC3T3-E1 osteoblasts were treated with NFkappaB inhibitor BAY 11-7082 and sc791 (a selective COX-2 inhibitor), in the presence of LPS. Interestingly, LPS could induce osteoblasts proliferation through increasing NFkappaB activation and translocation. This induction was not related to COX-2 expression, suggesting that LPS-induced NFkappaB activation is independent of COX-2. It is possible that low concentration of LPS can act as a stimulating factor of the NFkappaB pathway in nonstimulated cells such as osteoblasts. COX-2 is not necessary for the NFkappaB pathway during LPS-induced proliferation of osteoblasts since sc791 had no effects on this induction. These studies provide insight into a potential mechanism by which LPS can affect bone tissue repair in the initial phase of inflammation. 2009 John Wiley & Sons, Ltd.