Elastogenic Protein Expression of a Highly Elastic Murine Spinal Ligament: The Ligamentum Flavum

Spinal ligaments, such as the ligamentum flavum (LF), are prone to degeneration and iatrogenic injury that can lead to back pain and nerve dysfunction. Repair and regeneration strategies for these tissues are lacking, perhaps due to limited understanding of spinal ligament formation, the elaboration of its elastic fibers, maturation and homeostasis. Using immunohistochemistry and histology, we investigated murine LF elastogenesis and tissue formation from embryonic to mature postnatal stages. We characterized the spatiotemporal distribution of the key elastogenic proteins tropoelastin, fibrillin-1, fibulin-4 and lysyl oxidase. We found that elastogenesis begins in utero with the microfibril constituent fibrillin-1 staining intensely just before birth. Elastic fibers were first detected histologically at postnatal day (P) 7, the earliest stage at which tropoelastin and fibulin-4 stained intensely. From P7 to P28, elastic fibers grew in diameter and became straighter along the axis. The growth of elastic fibers coincided with intense staining of tropoelastin and fibulin-4 staining, possibly supporting a chaperone role for fibulin-4. These expression patterns correlated with reported skeletal and behavioral changes during murine development. This immunohistochemical characterization of elastogenesis of the LF will be useful for future studies investigating mechanisms for elastogenesis and developing new strategies for treatment or regeneration of spinal ligaments and other highly elastic tissues

Clinical analysis of thoracic ossified ligamentum flavum without ventral compressive lesion

The aim of this study was to analyze the clinical characteristics of thoracic ossified ligamentum flavum (OLF) and to elucidate prognostic factors as well as effective surgical treatment modality. The authors analyzed 106 thoracic OLF cases retrospectively from January 1999 to December 2008. The operative (n = 40) and the non-operative group (n = 66) were diagnosed by magnetic resonance imaging (MRI) and/or computed tomography (CT) imaging. We excluded cases exhibiting ventral compressive lesions causing subarachnoid space effacement in thoracic vertebrae as well as those with a coexisting cervical compressive myelopathy. Those in the operative group were treated with decompressive laminectomy as well as resection of OLF. The preoperative neurologic status and postoperative outcomes of patients, as indicated by their modified Japanese Orthopedic Association (mJOA) scores and recovery rate (RR), Modic changes, the axial (fused or non-fused) and sagittal (omega or beak) configurations of OLF, and the ratios of the cross-sectional area (CSA) and anteroposterior diameter (APD) of the most compressed level were studied. The most commonly affected segment was the T10–11 vertebral body level (n = 49, 27.1%) and the least affected segment was the T7–8 level (n = 1, 0.6%). The ratios of the CSA in non-fused and fused types were 77.3 and 59.3% (p < 0.001). When Modic changes were present with OLF, initial mJOA score was found to be significantly lower than those without Modic change (7.62 vs. 9.09, p = 0.033). Neurological status improved after decompressive laminectomy without fusion (preoperative vs. last mJOA; 7.1 ± 2.01 vs. 8.57 ± 1.91, p < 0.001). However, one patient exhibited transient deterioration of her neurological status after surgery. In the axial configuration, fused-type OLF revealed a significant risk for a decreased postoperative mJOA score (0–7, severe and moderate) (Odds ratio: 5.54, χ2 = 4.41, p = 0.036, 95% CI: 1.014–30.256). The results indicated that the new categorization of axial-type of OLF is a helpful predictor of postoperative patient outcome and fused type was related with poor prognosis. In OLF cases free from ventral lesions compressing the spinal cord, decompressive laminectomy is enough for successful surgical outcome. Therefore, early surgical treatment will be considered in cases with fused-type OLF compressing spinal cord even though they do not have myelopathic symptoms