MicroRNA-146a reduces IL-1 dependent inflammatory responses in the intervertebral disc.

Because miR-146a expression in articular chondrocytes is associated with osteoarthritis (OA), we assessed whether miR-146a is linked to cartilage degeneration in the spine. Monolayer cultures of nucleus pulposus (NP) cells from the intervertebral discs (IVD) of bovine tails were transfected with a miR-146a mimic. To provoke inflammatory responses and catabolic extracellular matrix (ECM) degradation, cells were co-treated with interleukin-1 (IL-1). Transfection of miR-146a decreases IL-1 induced mRNA levels of inflammatory genes and catabolic proteases in NP cells based on quantitative real-time reverse transcriptase PCR (qRT-PCR) analysis. Similarly, miR146a suppresses IL-1 induced protein levels of matrix metalloproteinases and aggrecanases as revealed by immunoblotting. Disc segments from wild type (WT) and miR-146a knockout (KO) mice were cultured ex vivo in the presence or absence of IL-1 for 3days. Histological and immuno-histochemical (IHC) analyses of disc organ cultures revealed that IL-1 mediates changes in proteoglycan (PG) content and in-situ levels of catabolic proteins (MMP-13 and ADAMTS-5) in the nucleus pulposus of the disc. However, these IL-1 effects are more pronounced in miR-146a KO discs compared to WT discs. For example, absence of miR-146a increases the percentage of MMP-13 and ADAMTS-5 positive cells after treatment with IL-1. Thus, miR-146a appears to protect against IL-1 induced IVD degeneration and inflammation. Stimulation of endogenous miR-146a expression or exogenous delivery of miRNA-146a are viable therapeutic strategies that may decelerate disc degeneration and regain a normal homeostatic balance in extracellular matrix production and turn-over.

Adapted simplified Chinese (mainland) version of Scoliosis Research Society-22 questionnaire.

STUDY DESIGN: Validation study to define validity and reliability of an adapted and translated questionnaire. OBJECTIVE: This study attempted to validate the traditional Chinese (Hong Kong) version of the modified Scoliosis Research Society (SRS) Outcomes Instrument, SRS-22, into simplified Chinese for use in mainland China. SUMMARY OF BACKGROUND DATA: Although a traditional Chinese (Hong Kong) adaptation of the SRS-22 has been previously validated, no culturally adapted, validated SRS-22 exists for use in mainland China. METHODS: Adhering to International Quality of Life Assessment Project guidelines, the adapted traditional Chinese SRS-22 was translated into simplified Chinese while referencing the original English questionnaire. To examine the psychometric properties and clinical application of the adapted simplified Chinese SRS-22, a survey was conducted in a group of randomly selected 87 patients previously surgically treated at an outpatient clinic. Reliability assessment of the simplified Chinese version of the SRS-22 was determined by calculating Cronbach's alpha and intraclass coefficient (ICC) values. Concurrent validity was evaluated by comparing SRS-22 domains with relevant domains of the simplified Short-Form-36 questionnaire; correlation was made using Pearson correlation coefficients. RESULTS: Cronbach's alpha, applied to each of the 22 questions of the adapted SRS-22, revealed very satisfactory internal consistency (Cronbach's alpha = 0.80-0.89) for function/activity and pain, and good consistency (Cronbach's alpha = 0.50-0.79) for the remaining domains. The test/retest reproducibility was found to be good (ICC > or =0.40-0.75) in the function/activity domain, and excellent (ICC > or =0.75) in the remaining domains. In terms of concurrent validity, 3 domains had excellent correlation, while 10 had good correlation, and 21 had moderate correlation. DISCUSSION: The authors report the validation of a simplified Chinese SRS-22 for use in mainland China, which is culturally relevant, reliable, repeatable, psychometrically sound, and suitable for immediate clinical use.

Abnormal ossification as a cause the progression of adolescent idiopathic scoliosis.

Although, there is no generally accepted scientific theory for the etiology of adolescent idiopathic scoliosis (AIS), the relative anterior spinal column overgrowth has been postulated as a mechanism of AIS progression by many morphological studies. The normal spinal growth involves both kinds of ossification: endochondral and membranous ossification. Considering the uncoupled anterior-posterior column growth of AIS patients, the uncoupled endochondral-membranous ossification could possibly play an important role in the progression of AIS. Meanwhile, other observations found that the uncoupling of ossification was not limited to the spinal column, but rather a systemic phenomenon. This consideration leads us to carefully dissect the underlying abnormal molecular pathways, cytokines or receptors of ossification, such as BMP-Smads, Runx2, FGFR-3, and will raise the hope to detect the AIS progression potentiality and help to formulate the appropriately personalized treatment strategy for patients.

Posterior pedicle screws combined with shortening and release techniques for lumbar and thoracolumbar adolescent idiopathic scoliosis.

OBJECTIVE: To prospectively evaluate the clinical and radiographic effects of posterior surgery with wide posterior shortening release and segmental pedicle screws techniques in a consecutive group of patients with thoracolumbar /lumbar adolescent idiopathic scoliosis. METHODS: Between April 2002 and July 2005, 114 patients (86 women and 28 men) were enrolled in this study. There were 72 Lenke type 5, 32 Lenke type 6, and 10 Lenke type 3C curves. Radiographic parameters such as coronal plane Cobb angle; lordosis angle; lowest instrumented vertebrae (LIV) angulation; and the distances from the central sacral vertical line (CSVL) to the LIV, to the apical vertebra and to the C7 plumb line, were analyzed. Complication rates were also recorded during follow-up. RESULTS: The average coronal correction was from 61° to 13° (78.6%). In the sagittal plane, lumbar lordosis was normalized from 36° with a wide range (23°-67°) to 42° with a normal range (34°-55°). The LIV had 79% correction of coronal angulations. The center sacral line to LIV was improved from 2.3 cm to 0.5 cm, apex to center sacral line from 5.0 cm to 1.6 cm, and CSVL from 2.7 cm to 0.8 cm. A total of 1460 pedicle screws were placed safely, average 9.6 levels (5-14) were fused. The patients were followed up for an average of 30 months (range, 12-50). There was excellent maintenance of correction at final follow-up. CONCLUSION: Wide posterior release and segmental pedicle screw instrumentation has excellent radiographic and clinical results with minimal complications.

[Analysis of the parameters about selective anterior fusion of thoracolumbar/lumbar curves in adolescent idiopathic scoliosis].

OBJECTIVE: To establish criteria for AIS of Lenke5 and Lenke6 by an anterior only procedure of the lower curve fusion. METHODS: A retrospective study was conducted between March 1999 and May 2004 to investigate 52 AIS patients of Lenke5 and Lenke6. All the patients were observed 24 years (34 months on average). Many parameters were evaluated. At final assessment, two groups emerged: Group A had satisfactory results (the thoracic curve was reduced) and Group B had just the opposite. RESULTS: Preoperative thoracic curve in group A averaged 33 degrees and 18 degrees after surgery. The lumbar curve averaged 49 degrees before surgery and 21 degrees after surgery. In group B (n = 6), the average thoracic curve was 38 degrees before surgery and 45 degrees after surgery, whereas the lumbar curve averaged 46 degrees before surgery and 25 degrees after surgery. Two of these patients underwent posterior thoracic instrumentation and fusion because of the unreasonable balance. CONCLUSIONS: A successful surgical outcome was dependent on both the flexibility of the thoracic curve and the patients' maturity. The thoracolumbar/lumbar-thoracic (TL/L:T) Cobb ratio in combination with the flexibility of the thoracic curve were the best predictors among the structural indexes.