ABSTRACT
BACKGROUND: Ossification of the ligamentum flavum overlying the lower thoracic spine frequently produces myelopathy. This study analyzed the postoperative outcomes after decompressive laminectomy for thoracic OLF. METHODS: We retrospectively studied 13 patients (10 male, 3 female; mean age, 58 years; range, 39-69). The mean follow-up duration was 66 months (range, 21-107). All patients had undergone decompressive laminectomy and excision of the OLF. The clinical course was evaluated according to the Frankel grading system and JOA scores. The number of vertebral segments demonstrating OLF, the most frequent level of thoracic cord involvement, and spine lesions coexisting with OLF were determined by MR imaging. RESULTS: By the Frankel system, 7 of 13 patients improved by one grade, whereas the others, classified as grade D, were unchanged after surgery. Using the JOA score, the functional improvement was excellent in 3 patients, good in 4, fair in 2, and unchanged in 4. The number of vertebral segments demonstrating OLF included 4 levels in 2 patients, 3 levels in 2 patients, 2 levels in 5 patients, and 1 level in 4 patients. Ossification of the ligamentum flavum occurred most frequently at the T10/T11 level. Tandem cervical and lumbar lesions were present in 6 patients. CONCLUSIONS: Decompressive laminectomy for excision of OLF resulted in clinical improvement using the Frankel grading system in 7 of 13 patients. In myelopathy patients with OLF, preoperative MR imaging of the entire spine is necessary because other coexisting spinal lesions may be present.
Subject(s)
Laminectomy , Ligamentum Flavum , Ossification, Heterotopic/complications , Spinal Cord Compression/surgery , Spinal Diseases/complications , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Ossification, Heterotopic/diagnosis , Ossification, Heterotopic/surgery , Retrospective Studies , Spinal Cord Compression/diagnosis , Spinal Cord Compression/etiology , Spinal Diseases/diagnosis , Spinal Diseases/surgery , Thoracic Vertebrae , Treatment OutcomeABSTRACT
Smad ubiquitin regulatory factor (Smurf) 1 binds to receptor-regulated Smads for bone morphogenetic proteins (BMPs) Smad1/5 and promotes their degradation. In addition, Smurf1 associates with transforming growth factor-beta type I receptor through the inhibitory Smad (I-Smad) Smad7 and induces their degradation. Herein, we examined whether Smurf1 negatively regulates BMP signaling together with the I-Smads Smad6/7. Smurf1 and Smad6 cooperatively induced secondary axes in Xenopus embryos. Using a BMP-responsive promoter-reporter construct in mammalian cells, we found that Smurf1 cooperated with I-Smad in inhibiting BMP signaling and that the inhibitory activity of Smurf1 was not necessarily correlated with its ability to bind to Smad1/5 directly. Smurf1 bound to BMP type I receptors via I-Smads and induced ubiquitination and degradation of these receptors. Moreover, Smurf1 associated with Smad1/5 indirectly through I-Smads and induced their ubiquitination and degradation. Smurf1 thus controls BMP signaling with and without I-Smads through multiple mechanisms.
Subject(s)
Activin Receptors, Type I/metabolism , Bone Morphogenetic Proteins/metabolism , DNA-Binding Proteins/metabolism , Receptors, Transforming Growth Factor beta/metabolism , Trans-Activators/metabolism , Ubiquitin-Protein Ligases/metabolism , Animals , COS Cells , Cells, Cultured , Embryo, Nonmammalian , Models, Molecular , Phosphorylation , Protein Binding , Protein Serine-Threonine Kinases , Receptor, Transforming Growth Factor-beta Type I , Recombinant Proteins , Signal Transduction , Smad6 Protein , Smad7 Protein , Xenopus , Xenopus ProteinsABSTRACT
Smad ubiquitin regulatory factor 1 (Smurf1), a HECT-type E3 ubiquitin ligase, interacts with inhibitory Smad7 and induces cytoplasmic localization of Smad7. Smurf1 then associates with transforming growth factor-beta type I receptor (TbetaR-I) and enhances the turnover of this receptor. However, the mechanisms of the nuclear export and plasma membrane localization of the Smurf1.Smad7 complex have not been elucidated. We show here that Smurf1 targets Smad7 to the plasma membrane through its N-terminal conserved 2 (C2) domain. Both wild-type Smurf1 (Smurf1(WT)) and Smurf1 lacking the C2 domain (Smurf1(deltaC2)) bound to Smad7 and translocated nuclear Smad7 to the cytoplasm. However, unlike Smurf1(WT), Smurf1(deltaC2) did not move to the plasma membrane and failed to recruit Smad7 to the cell surface TbetaR-II.TbetaR-I complex. Moreover, although Smurf1(deltaC2) induced ubiquitination of Smad7, it failed to induce the ubiquitination and degradation of TbetaR-I and did not enhance the inhibitory activity of Smad7. Thus, these results suggest that the plasma membrane localization of Smad7 by Smurf1 requires the C2 domain of Smurf1 and is essential for the inhibitory effect of Smad7 in the transforming growth factor-beta signaling pathway.