血红素加氧酶1对炎性细胞因子介导的保护作用

Osteoarthritis (OA) is a chronic degenerative joint disease showing altered bone metabolism. Osteoblasts
contribute to the regulation of cartilage metabolism and bone remode领. We have shown previously
that induction of heme oxygenase-1 (HO-1) protects OA cartilage against inflammatory and degradative
responses. In this study, we investigated the effects of HO-1 induction on OA osteoblast metabolism. HO-
1 was induced with cobalt protoporphyrin IX (CoPP) and by transduction with LV-HO-1. In osteoblasts
stimulated with interleukin (IL)-1b, CoPP enhanced mineralization, the expression of a number of
markers of osteoblast differentiation such as Runx2, bone morphogenetic protein-2, osteocalcin, and
collagen 1A1 and 1A2, as well as the ratio osteoprotegerin/receptor activator of nuclear factor-kB ligand.
HO-1 induction significantly reduced the expression of matrix metalloproteinase (MMP)-1, MMP-2 and
MMP-3, and the production of pro-inflammatory cytokines such as tumor necrosis factor-a and IL-6
whereas IL-10 levels increased. HO-1 also exerted inhibitory effects on prostaglandin (PG)E2 production
which could be dependent on cyclooxygenase-2 and microsomal PGE synthase-1 down-regulation. The
activity of senescence-associated b-galactosidase and the expression of the senescence marker caveolin-
1 were significantly decreased after HO-1 induction. The inhibition of nuclear factor-kB activation
induced by IL-1b in OA osteoblasts may contribute to some HO-1 effects. Our results have shown that
HO-1 decreases the production of relevant inflammatory and catabolic mediators that participate in OA
pathophysiology thus eliciting protective effects in OA osteoblasts.