Expression changes of IL-17 in zoledronic acid combined with PVP technology in the treatment of postmenopausal osteoporotic vertebral compression fracture and its predictive value of relapse.

OBJECTIVE: To investigate the expression of interleukin-17 (IL-17) in zoledronic acid combined with PVP technology for patients with postmenopausal osteoporotic vertebral compression fracture (OVCF) and its predictive value for relapse. METHODS: 101 OVCF patients treated in our hospital from April 2013 to January 2015 were collected as a research group and treated by zoledronic acid combined with PVP technology. 80 healthy people with physical examination were assigned to the control group. ELISA was used to detect the expression of IL-17 in serum of the two groups. Patients were followed up for 2 years. The expression of IL-17 before treatment was compared between patients with relapse and patients without relapse. The predictive value of IL-17 in relapse was drawn according to ROC curve. RESULTS: Before treatment, the expression of IL-17 in the research group increased significantly (p<0.05). After treatment, the expression of IL-17 in the research group decreased significantly (p<0.05). The level of IL-17 in patients with relapse was significantly higher than that in patients without relapse (p<0.05). CONCLUSIONS: IL-17 is highly expressed in postmenopausal patients with osteoporotic vertebral compression fracture and is expected to be a potential predictor of relapse in postmenopausal patients with OVCF.

PGE1 Attenuates IL-1ß-induced NGF Expression in Human Intervertebral Disc Cells.

STUDY DESIGN: In vitro study using isolated human intervertebral disc (IVD) cells. OBJECTIVE: To investigate the effects of prostaglandin (PG)E1 and its orally available derivative limaprost on the regulation of nerve growth factor (NGF) expression and to compare their actions with other prostanoids using interleukin (IL)-1-stimulated human IVD cells. SUMMARY OF BACKGROUND DATA: We previously reported that a selective COX-2 inhibitor enhanced, whereas PGE2 suppressed the induction of NGF by IL-1 in human IVD cells, and proposed that PGE2 can suppress NGF expression by a negative feedback mechanism. METHODS: Isolated human IVD cells were stimulated with IL-1 in the presence or absence of increasing concentrations of PGE2, PGE1, limaprost, PGI2, PGD2, or PGF2α (10-10,000 nM). For some experiments, an E-series prostanoid receptor (EP)4 antagonist (L-161,982) was added prior to the stimulation. NGF expression was determined by real-time polymerase chain reaction and its protein level was quantified by enzyme-linked immunosorbent assay. RESULTS: PGE2, PGE1, and limaprost inhibited the IL-1-mediated induction of NGF in a concentration-dependent manner, with IC50 values of 9.9, 10.6, and 70.9 nM, respectively. PGI2 also suppressed NGF expression but to a much less extent. PGD2, on the other hand, significantly enhanced NGF expression, whereas PGF2α had no effect. Protein expression levels of NGF mirrored its mRNA levels. The suppression of NGF expression by PGE2 and PGE1 was partly reversed by L-161,982. CONCLUSION: PGE1 and limaprost exhibited a novel pharmacological action that suppresses NGF expression in human IVD cells, and other prostanoids differentially regulated NGF expression. Limaprost has been used to treat patients with lumbar spinal stenosis in Japan and was proved to be effective in relieving symptoms. Our in vitro results may explain, in part, the mechanism of action of limaprost for low back pain. LEVEL OF EVIDENCE: N/A.

Regulation of nerve growth factor by anti-inflammatory drugs, a steroid, and a selective cyclooxygenase 2 inhibitor in human intervertebral disc cells stimulated with interleukin-1.

STUDY DESIGN: Regulation of nerve growth factor (NGF) by 2 different anti-inflammatory drugs was investigated in vitro using isolated human intervertebral disc (IVD) cells stimulated with the proinflammatory cytokine interleukin-1 (IL-1). OBJECTIVE: To investigate the regulation of NGF by a synthetic steroid and a selective cyclooxygenase-2 (COX-2) inhibitor and to clarify the biological role of prostaglandin E2 (PGE2) in this process. SUMMARY OF BACKGROUND DATA: NGF is known to play an important role in pain, including low back pain, and to be induced by proinflammatory cytokines in IVD cells. However, the effect of clinically used drugs for managing low back pain on the regulation of NGF is unclear. METHODS: Isolated human IVD cells were stimulated with interleukin-1 (IL-1) in the presence or absence of dexamethasone or a selective COX-2 inhibitor (NS-398). NGF expression and release were determined by real-time polymerase chain reaction and enzyme-linked immuno sorbent assay, respectively. Inhibition of PGE2 release was determined by enzyme-linked immuno sorbent assay. The effects of exogenous PGE2 and its receptor (E-series prostanoid receptors [EPs] 1-4) agonists were also tested for NGF regulation. RESULTS: IL-1 transiently induced, in a dose-dependent manner, the induction of NGF in human IVD cells. Pretreatment with dexamethasone strongly inhibited the NGF expression, whereas NS-398 significantly enhanced it at the concentration at which PGE2 release was substantially inhibited. Exogenous PGE2 inhibited IL-1 induction of NGF and this effect was mimicked when EP2 and EP4, but not EP1 and EP3, agonists were supplemented to the culture. CONCLUSION: Although selective COX-2 inhibitors have been shown to be effective for acute low back pain by inhibiting PGE2 release, our findings suggest that it may have a limited efficacy because it exaggerated NGF expression, whereas dexamethasone inhibited it. On the other hand, PGE2 had an inhibitory function for NGF induction by mediating EP2/4 in human IVD cells. Further studies are needed to clarify whether these observations could take place in vivo. LEVEL OF EVIDENCE: N/A.