RESUMEN
<p><b>BACKGROUND</b>The cannabinoid receptor-2 (CB2) is important for bone remodeling. In this study, we investigated the effects of CB2 selective antagonist (AM630) on receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) induced osteoclast differentiation and the underlying signaling pathway using a monocyte-macrophage cell line-RAW264.7.</p><p><b>METHODS</b>RAW264.7 was cultured with RANKL for 6 days and then treated with AM630 for 24 hours. Mature osteoclasts were measured by tartrate-resistant acid phosphatase (TRAP) staining using a commercial kit. Total ribonucleic acid (RNA) was isolated and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was done to examine the expression of RANK, cathepsin K (CPK) and nuclear factor kappa B (NF-κB). The extracellular signal-regulated kinase (ERK), phosphorylation of ERK (P-ERK) and NF-κB production were tested by Western blotting. The effect of AM630 on RAW264.7 viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay.</p><p><b>RESULTS</b>AM630 did not affect the viability of RAW264.7. However, this CB2 selective antagonist markedly inhibited osteoclast formation and the inhibition rate was dose-dependent. The dose of ≥ 100 nmol/L could reduce TRAP positive cells to the levels that were significantly lower than the control. AM630 suppressed the expression of genes associated with osteoclast differentiation and activation, such as RANK and CPK. An analysis of a signaling pathway showed that AM630 inhibited the RANKL-induced activation of ERK, but not NF-κB.</p><p><b>CONCLUSION</b>AM630 could inhibit the osteoclastogenesis from RAW264.7 induced with RANKL.</p>
Asunto(s)
Animales , Ratones , Western Blotting , Diferenciación Celular , Línea Celular , Supervivencia Celular , Indoles , Farmacología , Osteoclastos , Biología Celular , Metabolismo , Ligando RANK , Farmacología , Receptor Cannabinoide CB2 , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de SeñalRESUMEN
<p><b>OBJECTIVE</b>To evaluate the long-term clinical results and the factors that influences the outcomes of the revision open lumbar discectomy by fenestration.</p><p><b>METHODS</b>Fifty-one patients, who underwent the second open discectomy by fenestration from January 1 1988 to December 31 1994, were followed for an average of 146.8 months (range, 120 to 203 months). The long-term follow-up results were evaluated by using the MacNab classification and the Japanese Orthopaedic Association (JOA) scoring system through direct examinations and questionnaires. Radiography was also used in patients who agreed to visit the hospital, and findings were compared with those on preoperative radiographs.</p><p><b>RESULTS</b>At the final follow-up, with the MacNab classification an excellent and good outcome was achieved in 70.6% of the cases, 78.4% were satisfied with their results. The failure rate was 15.7% (8 patients). Excluding those 8 failed cases who needed another reoperation, the average improvement calculated by JOA scores was (64.6 +/- 18.2)%. The disc height of the operation site significantly decreased after surgery, nevertheless, this did not affect the long-term clinical outcome. Factors that were associated with a fair and bad outcome included smoking, isolated trauma or injury, fibrosis and the length of the remaining or recurrent primary postoperative symptoms history. Psychosociological signs were probably known as negative predictors of lumbar disc surgery outcome.</p><p><b>CONCLUSION</b>The long-term outcome of the revision open lumbar discectomy by fenestration in this series was favorable. Because the revision operation is typically associated with a higher complexity, selection of suitable surgical candidates and determination of valid indications for operative treatment are very important. JOA scores have proved to be easy to perform for patients and clinicians and standardize subjective data.</p>