The GH receptor (GHR) is a member of the cytokine receptor family. Short isoforms resulting from alternative splicing have been reported for a number of proteins in this family. RT-PCR experiments, in human liver and cultured IM-9 cells, using primers in exon 7 and 10 of the GHR, revealed three bands reflecting alternative splicing of GHR mRNA: the predicted product at 453 bp and two other products at 427 and 383 bp. The 427-bp product (GHR1-279) utilized an alternative 3'-acceptor splice site 26 bp downstream in exon 9; the predicted C-terminal residues are six frameshifted exon 9 codons ending in an inframe stop codon. The 383-bp product (GHR1-277) resulted from skipping of exon 9; the predicted C-terminal residues are three frame-shifted exon 10 codons ending in an in-frame stop codon. RNase protection experiments confirmed the presence of the GHR1-279 variant in IM-9 cells and human liver. The proportion of alternative splice to full length was 1-10% for GHR1-279 and less than 1% for GHR1-277. The function of GHR1-279 was examined after subcloning in an expression vector and transient transfection in 293 cells. Scatchard analysis of competition curves for [125l]-hGH bound to cells transfected either with GHR full length (GHRfl) or GHR1-279 revealed a 2-fold reduced affinity and 6-fold increased number of binding sites for GHR1-279. The increased expression of GHR1-279 was confirmed by cross-linking studies. The media of cells transfected with GHR1-279 contained 20-fold more GH-binding protein (GHBP) than that found in the media of cells transfected with the full-length receptor. Immunoprecipitation and Western blotting experiments, using a combination of antibodies directed against extracellular and intracellular GHR epitopes, demonstrated that GHRfl and GHR1-279 can form heterodimers and that the two forms also generate a 60-kDa GHBP similar in size to the GHBP in human serum. Functional tests using a reporter gene, containing Stat5-binding elements, confirmed that while the variant form was inactive by itself, it could inhibit the function of the full-length receptor. We have demonstrated the presence of a splice variant of the GHR in human liver encoding a short form of the receptor similar in size to a protein previously identified in human liver and choroid plexus. Expression studies in 293 cells support the hypothesis that while the expression of the splice variant accounts for only a small proportion of the total GHR transcript, it produces a short isoform that modulates the function of the full-length receptor, inhibits signaling, and generates large amounts of GHBP. The differential expression of GHR receptor short forms may regulate the production of GHBP, and truncated receptors may act as transport proteins or negative regulators of GHR signaling.

Anterior debridement and bone grafting with posterior instrumentation may not be the best choice for treating patients with spinal tuberculosis. Single posterior debridement/bone grafting/instrumentation for single-segment of thoracic or lumbar spine tuberculosis produced good clinical results, except in patients who had a psoas abscess.

The precise role of nucleus pulposus cell proliferation in the pathogenesis of intervertebral disc degeneration remains to be elucidated. Recent findings have revealed that microRNAs, a class of small noncoding RNAs, may regulate cell proliferation in many pathological conditions. Here, we showed that miR-21 was significantly upregulated in degenerative nucleus pulposus tissues when compared with nucleus pulposus tissues that were isolated from patients with idiopathic scoliosis and that miR-10b levels were associated with disc degeneration grade. Moreover, bioinformatics target prediction identified PTEN as a putative target of miR-21. miR-21 inhibited PTEN expression by directly targeting the 3′UTR, and this inhibition was abolished through miR-21 binding site mutations. miR-21 overexpression stimulated cell proliferation and AKT signaling pathway activation, which led to cyclin D1 translation. Additionally, the increase in proliferation and cyclin D1 expression induced by miR-21 overexpression was almost completely blocked by Ly294002, an AKT inhibitor. Taken together, aberrant miR-21 upregulation in intervertebral disc degeneration could target PTEN, which would contribute to abnormal nucleus pulposus cell proliferation through derepressing the Akt pathway. Our study also underscores the potential of miR-21 and the PTEN/Akt pathway as novel therapeutic targets in intervertebral disc degeneration.

Study design: Retrospective case-control study. Objectives: To analyze the results of two surgical treatments for lower lumbar tuberculous spondylitis with neurological deficits in the aged. Methods: We studied 33 cases of lower lumbar spinal tuberculous spondylitis treated in our center from January 2006 to October 2010. The cases were divided into two groups: 16 cases (group A) underwent single-or two-stage anterior debridement, bone grafting and posterior instrumentation, and 17 cases (group B) underwent single-stage posterior debridement, decompression, interbody fusion and instrumentation. Clinical and radiographic results were analyzed and compared between the groups. Results: Patients were followed for a mean of 41.3 months (range 36-48 months). The average operative durations were 276.9 ± 23.8 and 193.8 ± 22.5 min in groups A and B, respectively. The average hospital stay was 18.2 ± 3.2 days for group A and 13.4 ± 1.6 days for group B. Average intraoperative blood loss for groups A and B was 1187.5 ± 163.0 and 804.7 ± 134.1 ml, respectively. Operative complications affected four patients in group A and one in group B. Solid fusion occurred at 12 months in the other 32 cases. Neurological status was significantly improved in all cases. Kyphosis was significantly corrected after surgical management, but loss of correction occurred in both groups. Conclusion: Single-stage posterior debridement, decompression, interbody fusion and instrumentation might be a better surgical treatment than combined posterior and anterior approaches for lower lumbar tuberculous spondylitis with neurological deficits in the aged, offering fewer complications and a better quality of life.

BackgroundThere are quite a few controversies on the surgical management of single-segment thoracic spinal tuberculosis with neurological deficits (STSTND). In this study, the clinical efficacy and feasibility of one-stage posterior-only transpedicular debridement, interbody fusion, and posterior instrumentation for treating STSTND in adults were retrospectively evaluated.MethodsThirty-four cases with STSTND underwent one-stage posterior-only transpedicular debridement, interbody fusion and posterior instrumentation at the same institution from January 2003 to January 2013. Follow-up time was 34.4 ± 10.2 months (range, 18–48 months), and kyphosis angle was 34.1 ± 12.3°. The American Spinal Injury Association (ASIA) classification of spinal cord injury was employed to evaluate neurological deficits, while visual analogue scale (VAS) was employed to assess the degree of pain. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used to evaluate the activity of tuberculosis (TB).ResultsAll 34 patients with spinal tuberculosis (ST) were completely cured, and there was no recurrence of TB. Postoperative kyphosis angle was 8.2 ± 1.8°, and there was no significant loss of correction during the final follow-up. Solid fusion was achieved and pain was relieved in all cases. Neurological condition in all patients improved after surgery.ConclusionsOne-stage posterior-only transpedicular debridement, interbody fusion, and posterior fixation followed by chemotherapy seems to be adequate for obtaining satisfactory healing of single-segment thoracic spinal tuberculosis with neurological deficits. Careful patient selection is critical to the successful outcome with this technique.

With standardized anti-TB chemotherapy, thoracolumbar spinal tuberculosis with psoas abscesses could be effectively treated by one-stage posterior transforaminal lumbar debridement, interbody fusion, posterior instrumentation, and postural drainage.

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Our results suggest that one-stage posterior debridement, interbody fusion, lumbopelvic fixation, and postural drainage can be an effective and feasible treatment option for lumbosacral junction tuberculosis, offering fewer complications and a better quality of life.