KLF5 promotes the ossification process of ligamentum flavum by transcriptionally activating CX43.

BACKGROUND: Ossification of ligamentum flavum (OLF) is a prevalent degenerative spinal disease, typically causing severe neurological dysfunction. Kruppel-like factor 5 (KLF5) plays an essential role in the regulation of skeletal development. However, the mechanism KLF5 plays in OLF remains unclear, necessitating further investigative studies. METHODS: qRT-PCR, immunofluorescent staining and western blot were used to measure the expression of KLF5. Alkaline Phosphatase (ALP) staining, Alizarin red staining (ARS), and the expression of Runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcin (OCN) were used to evaluate the osteogenic differentiation. Luciferase activity assay and ChIP-PCR were performed to investigate the molecular mechanisms. RESULTS: KLF5 was significantly upregulated in OLF fibroblasts in contrast to normal ligamentum flavum (LF) fibroblasts. Silencing KLF5 diminished osteogenic markers and mineralized nodules, while its overexpression had the opposite effect, confirming KLF5's role in promoting ossification. Moreover, KLF5 promotes the ossification of LF by activating the transcription of Connexin 43 (CX43), and overexpressing CX43 could reverse the suppressive impact of KLF5 knockdown on OLF fibroblasts' osteogenesis. CONCLUSION: KLF5 promotes the OLF by transcriptionally activating CX43. This finding contributes significantly to our understanding of OLF and may provide new therapeutic targets.

Full endoscopic surgery for calcium pyrophosphate deposition disease (CPPD) in the cervical ligamentum flavum: report of two cervical myelopathy cases.

Calcium pyrophosphate deposition disease (CPPD), known as pseudogout, is characterized by the accumulation of calcium pyrophosphate crystals in musculoskeletal structures, primarily joints. While CPPD commonly affects various joints, involvement in the cervical spine leading to myelopathy is rare. Surgical intervention becomes necessary when conservative measures fail, but reports on full endoscopic surgeries are extremely rare. We present two successful cases where full endoscopic systems were used for CPPD removal in the cervical spine. The surgical technique involved a full endoscopic approach, adapting the previously reported technique for unilateral laminotomy bilateral decompression. Full-endoscopic removal of cervical CPPD inducing myelopathy were successfully removed with good clinical and radiologic outcomes. The scarcity of endoscopic cases for cervical ligamentum flavum CPPD is attributed to the condition's rarity. However, our successful cases advocate for endoscopic surgery as a potential primary treatment option for CPPD-induced cervical myelopathy, especially in elderly patients or those with previous cervical operation histories. This experience encourages the consideration of endoscopic surgery for managing cervical ligamentum flavum CPPD as a viable alternative.

Safety and efficacy of one-hole split endoscope technique for surgical treatment of thoracic ossification of the ligamentum flavum.

Surgical intervention is typically recommended for thoracic ossification of the ligamentum flavum (TOLF). This study aimed to evaluate the efficacy and safety of a novel non-coaxial one-hole split endoscope (OSE) technique for treating TOLF. We performed OSE procedure on 13 patients with TOLF from June 2022 to July 2023. The mean operative time was 117.5 ± 15.4 min. VAS scores for lower limbs decreased from 6.5 ± 0.8 preoperative to 1.6 ± 0.4 at the last follow-up (P < 0.001). ODI scores improved from 62.4 ± 5.7 preoperative to 18.6 ± 2.2 at the last follow-up (P < 0.001), and mJOA scores increased from 5.1 ± 1.6 preoperative to 8.4 ± 1.5 at the latest follow-up (P < 0.001). All patients achieved ASIA scale grade D or E at the final follow-up, except for two patients remained residual limb numbness. None of the thirteen patients suffered from severe perioperative complications. The OSE technique proves to be a safe and effective procedure for treating TOLF or even with dura mater ossification, characterized by minimal surgical trauma, relatively smooth learning curve and flexible operation.

Thrombospondin-1 promotes mechanical stress-mediated ligamentum flavum hypertrophy through the TGFß1/Smad3 signaling pathway.

Lumbar spinal canal stenosis is primarily caused by ligamentum flavum hypertrophy (LFH), which is a significant pathological factor. Nevertheless, the precise molecular basis for the development of LFH remains uncertain. The current investigation observed a notable increase in thrombospondin-1 (THBS1) expression in LFH through proteomics analysis and single-cell RNA-sequencing analysis of clinical ligamentum flavum specimens. In laboratory experiments, it was demonstrated that THBS1 triggered the activation of Smad3 signaling induced by transforming growth factor ß1 (TGFß1), leading to the subsequent enhancement of COL1A2 and α-SMA, which are fibrosis markers. Furthermore, experiments conducted on a bipedal standing mouse model revealed that THBS1 played a crucial role in the development of LFH. Sestrin2 (SESN2) acted as a stress-responsive protein that suppressed the expression of THBS1, thus averting the progression of fibrosis in ligamentum flavum (LF) cells. To summarize, these results indicate that mechanical overloading causes an increase in THBS1 production, which triggers the TGFß1/Smad3 signaling pathway and ultimately results in the development of LFH. Targeting the suppression of THBS1 expression may present a novel approach for the treatment of LFH.

Quantitative evaluation of the lumbar ligamentum flavum using MRI T2-mapping: Efficacy of its clinical application in patients with lumbar spinal stenosis.

OBEJECTIVE: To perform a magnetic resonance imaging T2-mapping of the ligamentum flavum in healthy individuals and patients with lumbar spinal stenosis scheduled for surgery and compare the T2 relaxation times. SUBJECTS AND METHODS: The T2 relaxation time of the ligamentum flavum was compared among 3 groups, healthy young individuals (H group (age< 50)), healthy middle-aged and older individuals (H group (age≥50)), and patients with lumbar spinal stenosis (L group). Additionally, the thickness of the ligament was measured in the axial image plane, and the occupied area ratio of each fiber was measured by staining the surgically obtained ligament, and each was correlated with the T2 relaxation time. We also evaluated the adhesion of the ligamentum flavum with the dura mater during the surgery. RESULTS: The T2 relaxation times were significantly prolonged in H group (age ≥50) and L group (P < 0.001) compared to H group (age<50). The relationship between collagen fiber and T2 relaxation times was significantly positive (r = 0.720, P < 0.001). Moreover, the relaxation times were significantly prolonged in those with adhesion of the ligamentum flavum with the dura mater (P < 0.05). The cut-off for the relaxation time was 50 ms (sensitivity: 62.50%, false positive rate: 10.8%). CONCLUSION: Healthy middle-aged and older individuals and patients with lumbar spinal stenosis and adhesion of the ligamentum flavum with the dura mater have prolonged T2 relaxation times. Hence, the adhesion between the ligamentum flavum and dura mater should be considered in cases with a relaxation time ≥50 ms.

Lumbar Spinous Process-Splitting Technique for Ligamentum Flavum Cyst Removal.

BACKGROUND: Laminotomy for lumbar stenosis is a well-defined procedure and represents a routine in every neurosurgical department. It is a common experience that the uni- or bilateral paraspinal muscle detachment, together with injury of the supra- and interspinous ligaments, can lead to postoperative pain. In the literature, the application of a minimally invasive technique, the lumbar spinous process-splitting (LSPS) technique, has been reported. METHODS: In this study, we present a case series of 12 patients who underwent LSPS from September 2019 to April 2020. Two patients had a cyst of the ligamentum flavum, eight a single-level lumbar canal stenosis (LCS), and two a two-level LCS. Moreover, we propose a novel morphological classification of postoperative muscle atrophy and present volumetric analysis of the decompression achieved. RESULTS: There were no complications related to this technique. In all patients, the vertebral canal area was more than doubled by the procedure. The muscle sparing showed grade A, according to our classification. CONCLUSION: To our knowledge, this is the first description of this surgical technique and the first LSPSL case series in Europe. Furthermore, cases of ligamentum flavum cyst removal using this safe and effective technique have not yet been reported.

The Quality of Life of the Patients with Thoracic Ossification of the Ligamentum Flavum after Surgery Using EQ-5D-5L.

OBJECTIVE: There is a lack of studies on the quality of life (QoL) after posterior laminectomy in patients with thoracic ossification of the ligamentum flavum (TOLF), and risk factors associated with poor prognosis remain controversial. Therefore, the present study was conducted to illustrate the QoL for TOLF patients after surgery and determine its relationship with their demographic, surgery-related, clinical characteristics and imaging data. METHODS: One hundred and eighteen patients diagnosed with thoracic myelopathy because of TOLF were enrolled in this retrospective study. They all underwent posterior decompressive laminectomy from August 2010 to January 2022. The QoL was evaluated based on the EQ-5D-5L. Collecting gender, age, number of operations, compressed segments, Frankel grade, complications, body mass index (BMI), symptoms and duration, modified Japanese Orthopaedic Association (mJOA) score (preoperative), follow-up time and type of ossification, increased signal on Sagittal T2-weighted Images (ISST2I), occupancy rate and analyzing by Mann-Whitney U-test, Kruskal-Wallis test, the χ2 -test, and logistic regression tests. RESULTS: Average follow-up 70.8 months (18-149), the mean age was 59.74 ± 9.81 years and the mean score for the QoL based on the EQ-5D-5 L and visual analogue scale (VAS) score were 0.71 ± 0.28 and 78.88 ± 10.21 at the final follow-up. Moderate and severe problems were found in the pain/discomfort in 22.0% of the patients. These mobility and usual activities numbers were slightly higher (24.6% and 30.4%, respectively). The mean scores for QoL and VAS were significantly higher in patients with mild and moderate neurological impairment, normal BMI, <60 years of age, no dural tears, symptom relief at hospital discharge, unilateral and bilateral ossification on axial CT scan, ≤ 50% spinal canal occupancy on CT and MRI, and none or fuzzy on ISST2I. CONCLUSION: QoL after posterior laminectomy in TOLF patients is generally satisfactory compared to preoperative levels. Preoperative mJOA score, Age, comorbid diabetes, the major symptom is activity limitation, BMI, ISST2I, Intraoperative dural tears and spinal canal occupancy rate correlate significantly with the corresponding dimensions and are predictive. Age, spinal canal occupancy rate, ISST2I, preoperative mJOA score, BMI are significantly associated with and have predictive value for overall postoperative QoL.

Safety and Efficacy Outcomes Following Spinal Endoscopic Procedures for Thoracic Ligamentous Ossification: A Systematic Review and Meta-Analysis.

STUDY DESIGN: A systematic review and meta-analysis. OBJECTIVE: This study systematically reviewed and evaluated the safety and efficacy of spinal endoscopic techniques as a treatment for thoracic ligamentum flavum ossification (TOLF). SUMMARY OF BACKGROUND DATA: The use of spinal endoscopic techniques for the treatment of TOLF has increased in recent years. The present study is the first comprehensive systematic review and meta-analysis focused on the use of spinal endoscopic techniques for TOLF. MATERIALS AND METHODS: The Cochrane Central, PubMed, Web of Science, and Embase databases were systematically searched for studies focused on patients undergoing spinal endoscopic techniques to treat symptomatic TOLF. RESULTS: This meta-analysis included 23 studies. We included 323 patients (177 males, 146 females) with a mean age of 58.40±10.06 years, with 304 total recorded lesion locations of which 245 were located in the lower thoracic spine. Complications affected 35/323 patients, and the mean operative duration for 305 patients was 108.15±47.34 minutes. For 187 patients, the mean operative bleeding was 25.13±12.54 mL, while for 87 patients the mean duration of hospitalization was 4.59±1.93 days. At last follow-up, functional assessment was performed for 260 patients, of whom 200 were in excellent condition, visual analog scale (VAS) scores were assessed for 160 patients, with a mean improvement of 4.40 (3.95, 4.86) Japanese Orthopedic Association (JOA) scores were recorded for 115 patients, with a mean improvement of 3.49 (2.79,4.18), and modified Japanese Orthopedic Association (mJOA) scores were recorded for 208 patients, with a mean improvement of 3.62 (2.89,4.35). CONCLUSIONS: These results support several advantages of spinal endoscopic techniques for the treatment of symptomatic TOLF. These include low complication rates, rapid postoperative recovery, and good functional recovery when used for single-segment, non-nodular ossification and no combined dural ossification.

Evolution of sagittal spinal shape for the development of thoracic ossification of ligamentum flavum.

Thoracic ossification of the ligamentum flavum (TOLF) is a rare pathology for which limited research exists. While it is known that mechanical factors play a role in the development of TOLF, little is currently understood about the sagittal alignment and related mechanical stress involved in its development. This study aims to describe the sagittal alignment of patients with TOLF based on the pathologic evolution of the Roussouly classification. The current study evaluated the preoperative Roussouly type in consecutive patients who underwent posterior decompressive laminectomy with or without posterior screw fixation for TOLF between January 2015 and December 2021. The post-evolution sagittal alignments were analyzed using the classic Roussouly classification based on sacral slope (SS). To determine the pre-evolution Roussouly type, the patients were retrospectively classified using their individual PI and PT values. Lumbopelvic parameters and morphological index including inflection point (IP), lumbar apex (LA), and lordosis distribution index (LDI) were also evaluated. Forty-three patients (21 women and 22 men) were included; their mean age was 64.21 ±â€…11.01 years (range 43-81). The most affected level was T10-11 (48.83%). The mean PI was 50.81 ±â€…9.56°, the mean SS was 33.11 ±â€…8.61°and the mean PT was 17.69 ±â€…7.89°. According to the post-evolution Roussouly classification, type 2 shape was the most frequently observed type (n = 23, 53.5%) in the post-evolution classification while type 3 was the most common type observed in the pre-evolution classification (n = 22, 51.5% and P = .00). The level of IP and LA in type 3 moved caudally (around L2 and L4/5 level, respectively) and the LDI increased (77.98 ±â€…8.08%) than the normal standard value. The authors found that the majority of the patients had a false type 2 spine, which had evolved pathologically from Roussouly type 3 and exhibited increased LDI, a lowered level of IP, and a lowered level of LA. These changes of spinal shape, including the transition to long hypolordosis and increased length of the thoracic kyphosis, may have accentuated tensile stress at the lower thoracic spine and contributed to the development of TOLF.

Lamina-Lifting Suspension Modification in Bridge Crane Technique in Treatment of Severe Thoracic Ossification of the Ligamentum Flavum (TOLF).

BACKGROUND The aim of this study was to investigate the effectiveness and potential complications of combining a lamina-lifting suspension system with the bridge crane technique in treating thoracic ossification of the ligamentum flavum (TOLF) with thoracic myelopathy. MATERIAL AND METHODS A patient with severe TOLF and myelopathy was treated using a lamina-lifting suspension system combined with bridge crane technique. The brief surgical procedure involved implantation of internal fixation, separation of laminae, installation of cross-bridges, reverse lifting, and fixation of cross-bridges. The modified Japanese Orthopaedic Association (mJOA) scale, Hirabayashi recovery rate, and ASIA grade of the patient were recorded. The canal occupation ratio (COR) and spinal cord status were evaluated by imaging data. RESULTS The surgical intervention significantly enhances the patient's lower limb function, as evidenced by an increase in mJOA score from 5 preoperatively to 11 at terminal follow-up. The Hirabayashi recovery rate after surgery ranges between 25% and 50%. Additionally, ASIA classification improved to grade E. Imaging data showed that the ossification of the thoracic vertebrae had subsided, while the volume of the local spinal canal had recovered and the spinal cord injury had been completely relieved. No adverse effects or complications were observed. CONCLUSIONS The lamina-lifting suspension system preserves the benefits of bridge crane technique while also augmenting the traction of a post laminae-OLF complex (LOC) suspension, rendering it more secure and manageable. Nevertheless, further sample analysis and research are required in the future.

ACSM5 inhibits ligamentum flavum hypertrophy by regulating lipid accumulation mediated by FABP4/PPAR signaling pathway.

BACKGROUND: Ligamentum flavum (LF) hypertrophy is the main cause of lumbar spinal canal stenosis (LSCS). Previous studies have shown that LF hypertrophy tissue exhibits abnormal lipid accumulation, but the regulatory mechanism remains unclear. The objective of this study was to explore the function and potential mechanism of ACSM5 in LF lipid accumulation. METHODS: To assess the ACSM5 expression levels, lipid accumulation and triglyceride (TG) level in LF hypertrophy and normal tissue, we utilized RT-qPCR, western blot, oil red O staining, and TG assay kit. The pearson correlation coefficient assay was used to analyze the correlation between ACSM5 levels and lipid accumulation or TG levels in LF hypertrophy tissue. The role of ACSM5 in free fatty acids (FFA)-induced lipid accumulation in LF cells was assessed in vitro, and the role of ACSM5 in LF hypertrophy in mice was verified in vivo. To investigate the underlying mechanisms of ACSM5 regulating lipid accumulation in LF, we conducted the mRNA sequencing, bioinformatics analysis, and rescue experiments. RESULTS: In this study, we found that ACSM5, which was significantly down-regulated in LF tissues, correlated with lipid accumulation. In vitro cell experiments demonstrated that overexpression of ACSM5 significantly inhibited FFA-induced lipid accumulation and fibrosis in LF cells. In vivo animal experiments further confirmed that overexpression of ACSM5 inhibited LF thickening, lipid accumulation, and fibrosis. Mechanistically, ACSM5 inhibited lipid accumulation of LF cells by inhibiting FABP4-mediated PPARγ signaling pathway, thereby improving hypertrophy and fibrosis of LF. CONCLUSIONS: our findings elucidated the important role of ACSM5 in the regulation of LF lipid accumulation and provide insight into potential therapeutic interventions for the treatment of LF hypertrophy. This study further suggested that therapeutic strategies targeting lipid deposition may be an effective potential approach to treat LF hypertrophy-induced LSCS.

Minimally invasive fenestration for decompression of C2-C3 spinal stenosis.

Conventional techniques in neurosurgery such as laminectomy have been extensively displaced by minimally invasive types, owing to the character of complexity of cervical spinal region. Spinal canal stenosis at C2-C3 level is documented in the literature with the majority being caused by intervertebral disc herniations.This case reports a patient who presented with classical myelopathy symptoms and significant thickening of ligamentum flavum, while minimal spondylosis was detected at C2-C3 level. The decompression was performed from posterior approach and limited to the removal of ligamentum flavum with minimal resection of adjacent laminae, no fixation and no disc evacuation. After surgery, there was a significant improvement with preserved spinal stability.Although the anterior approach is more common for cervical spine, universal access site has not been defined in literature. We suggest that minimal decompression produces desirable effects with no need for fusion and preserving adequate stability of spinal complex.

Transthyretin amyloid deposition in ligamentum flavum (LF) is significantly correlated with LF and epidural fat hypertrophy in patients with lumbar spinal stenosis.

Lumbar spinal stenosis (LSS) is a degenerative disease characterized by intermittent claudication and numbness in the lower extremities. These symptoms are caused by the compression of nerve tissue in the lumbar spinal canal. Ligamentum flavum (LF) hypertrophy and spinal epidural lipomatosis in the spinal canal are known to contribute to stenosis of the spinal canal: however, detailed mechanisms underlying LSS are still not fully understood. Here, we show that surgically harvested LFs from LSS patients exhibited significantly increased thickness when transthyretin (TTR), the protein responsible for amyloidosis, was deposited in LFs, compared to those without TTR deposition. Multiple regression analysis, which considered age and BMI, revealed a significant association between LF hypertrophy and TTR deposition in LFs. Moreover, TTR deposition in LF was also significantly correlated with epidural fat (EF) thickness based on multiple regression analyses. Mesenchymal cell differentiation into adipocytes was significantly stimulated by TTR in vitro. These results suggest that TTR deposition in LFs is significantly associated with increased LF hypertrophy and EF thickness, and that TTR promotes adipogenesis of mesenchymal cells. Therapeutic agents to prevent TTR deposition in tissues are currently available or under development, and targeting TTR could be a potential therapeutic approach to inhibit LSS development and progression.

PTGR1 is involved in cell proliferation in thoracic ossification of the ligamentum flavum.

Thoracic ossification of the ligamentum flavum (TOLF) is a heterotopic ossification of spinal ligaments, leading to serious myelopathy. TOLF underlying mechanisms are not well understood. Our iTRAQ analysis have identified ten inflammatory factors related to TOLF, including l. We found that PTGR1 expressions increased in TOLF by RT-PCR and western blot in this study. Both cell proliferation and differentiation are important for the process of bone formation. In our previous study, we demonstrated that TOLF primary cells grew faster than control cells. It was reported that knockdown of PTGR1 inhibited cell proliferation. We hypothesize that PTGR1 may participate in cell proliferation in TOLF. To test this hypothesis, TOLF primary cells were treated for 24h with PTGR1. We observed that PTGR1 increased cell proliferation. The effect of PTGR1 on cell proliferation related genes was examined in TOLF primary cells. Our results showed that PTGR1 was able to activate expressions of c-Myc and CyclinD1. Moreover, blocking JNK pathway by selective JNK inhibitor SP600125 eliminated the positive effect of PTGR1 on c-Myc expression, indicating that PTGR1 activated the expression of c-Myc via JNK pathway. Our new findings suggest that PTGR1 is involved in cell proliferation of TOLF.

The cervical ligamentum flavum area: A new sensitive morphological parameter for identifying the cervical spinal stenosis.

Thickening of the cervical ligamentum flavum (CLF) has been considered as a main cause of cervical spinal stenosis (CSS). A previous study reported that cervical ligamentum flavum thickness (CLFT) is correlated with CSS. However, the whole hypertrophy is different from focal thickness. Therefore, to analyze hypertrophy of the CLF, we created a new morphological parameter, called the cervical ligamentum flavum area (CLFA). We hypothesized that the CLFA is an important morphological parameter in the diagnosis of CSS. CLF samples were acquired from 83 patients with CSS, and from 84 controls who underwent cervical magnetic resonance imaging (C-MRI). T2-weighted axial C-MRI images were acquired. We measured the CLFA and CLFT at the C6-C7 intervertebral level on C-MRI using appropriate image analysis software. The CLFA was measured as the cross-sectional area of the entire CLF at the level of C6-C7 stenosis. The CLFT was measured by drawing a straight line along the ligament side towards the spinal canal at the C6-C7 level. Mean CLFA was 25.24 ±â€…6.43 mm2 in the control group and 45.34 ±â€…9.09 mm2 in the CSS group. The average CLFT was 1.48 ±â€…0.28 mm in the control group and 2.09 ±â€…0.35 mm in the CSS group. CSS patients had significantly higher CLFA (P < .01) and CLFT (P < .01). For the validity of both CLFA and CLFT as predictors of CSS, a receiver operating characteristic curve analysis revealed an optimal cutoff point for the CLFA was 31.66 mm2, a sensitivity of 92.8%, specificity of 88.4%, and an area under the curve of 0.97 (95% CI, 0.94-0.99). The optimal cut off-point of the CLFT was 1.79 mm, with a sensitivity of 83.5%, specificity of 84.5%, and an area under the curve of 0.92 (95% CI, 0.87-0.96). Both CLFT and CLFA were significantly related to CSS, but CLFA was the more sensitive measurement parameter. Therefore, to evaluate patients with CSS, treating physicians should test for CLFA.

The biomechanical effect of different types of ossification of the ligamentum flavum on the spinal cord during cervical dynamic activities.

Ossification of the ligamentum flavum (OLF) is thought to be an influential etiology of myelopathy, as thickened ligamentum flavum causes the stenosis of the vertebral canal, which could subsequently compress the spinal cord. Unfortunately, there was little information available on the effects of cervical OLF on spinal cord compression, such as the relationship between the progression of cervical OLF and nervous system symptoms during dynamic cervical spine activities. In this research, a finite element model of C1-C7 including the spinal cord featured by dynamic fluid-structure interaction was reconstructed and utilized to analyze how different types of cervical OLF affect principal strain and stress distribution in spinal cord during spinal activities towards six directions. For patients with cervical OLF, cervical extension induces higher stress within the spinal cord among all directions. From the perspective of biomechanics, extension leads to stress concentration in the lateral corticospinal tracts or the posterior of gray matter. Low energy damage to the spinal cord would be caused by the high and fluctuating stresses during cervical movements to the affected side for patients with unilateral OLF at lower grades.

Comparison of ligamentum flavum thickness between central and lateral lesions in a patient with central lumbar spinal canal stenosis.

Thickened ligamentum flavum has been considered as a major cause of central lumbar spinal canal stenosis (CLSCS). Previous studies have demonstrated that ligamentum flavum thickness (LFT) is correlated with aging, degenerative spinal stenosis, and disc degeneration. Thus, hypertrophy of the ligamentum flavum is a major cause of CLSCS, and measurement of LFT has been considered a morphologic parameter in the diagnosis of CLSCS. To our knowledge, comparison of LFT between central and lateral lesions has not been reported. In addition, no research has analyzed best clinical cutoff values of central ligament flavum thickness (CLFT) and lateral ligament flavum thickness (LLFT). This study aimed to compare CLFT with LLFT in patients with CLSCS and further compare the CLFT and LLFT findings between the 2 groups to analyze LFT variation. Both CLFT and LLFT samples were collected from 101 participants with CLSCS and from 103 participants in the control group who underwent lumbar magnetic resonance imaging without evidence of CLSCS. Axial T2-weighted lumbar magnetic resonance scans were acquired at the L4 to 5 facet joint level from each participant. Average CLFT value was 2.25 ± 0.51 mm in the control group and 4.02 ± 0.74 mm in the CLSCS group. Average LLFT value was 2.50 ± 0.51 mm in the control group and 3.38 ± 0.66 mm in the CLSCS group. CLSCS patients had significantly higher CLFT and LLFT (both P < .001). Regarding the validity of both CLFT and LLFT as predictors of CLSCS, a receiver operating characteristic estimation revealed that the most suitable cutoff value for CLFT was 3.10 mm, with sensitivity of 95.0%, specificity of 94.2%, and an area under the curve of 0.97. The best cut-off value of LLFT was 2.92 mm, with sensitivity of 78.2%, specificity of 77.7%, and area under the curve of 0.87. We have 4 important new findings: The mean CLFT is significantly lower than that of the mean LLFT in the normal control group; CLFT and LLFT are both significantly associated with CLSCS; Increase rate of CLFT is faster than that of LLFT in the CLSCS group; and CLFT is a more sensitive measurement parameter to predict CLSCS than LLFT.

Manipulation of osteogenic and adipogenic differentiation of human degenerative disc and ligamentum flavum derived progenitor cells using IL-1ß, IL-19, and IL-20.

PURPOSE: To elucidate whether pro-inflammatory cytokines might influence the commitment of intervertebral disc (IVD)- and ligamentum flavum (LF)-derived progenitor cells toward either osteogenesis or adipogenesis, specifically Interleukin-1ß (IL-1ß), IL-19, and IL-20. METHODS: Sixty patients with degenerative spondylolisthesis and lumbar or lumbosacral spinal stenosis were included in the study. Injuries to the spine, infections, and benign or malignant tumors were excluded. From nine patient samples, IVD- and LF-derived cells were isolated after primary culture, and two clinical samples were excluded due to mycoplasma infection. The effects of IL-1ß, IL-19, as well as IL-20 in regulating osteogenic and adipogenic differentiation in vitro were investigated. RESULTS: Primary IVD- and LF-derived cells were found to have a similar cell morphology and profile of surface markers (CD44, CD90, and CD105) as placenta-derived mesenchymal stem cells (MSCs). Primary IVD/LF cells have a high capacity to differentiate into osteocytes and adipocytes. IL-19 had a tendency to promote adipogenesis. IL-20 inhibited osteogenesis and promoted adipogenesis; IL-1ß promoted osteogenesis but inhibited adipogenesis. CONCLUSION: IL-1ß, IL-19, and IL-20 impact the adipogenic and osteogenic differentiation of IVD-derived and LF-derived cells. Modulating the expression of IL-1ß, IL-19, and IL-20 provides a potential avenue for controlling cell differentiation of IVD- and LF-derived cells, which might have beneficial effect for degenerative spondylolisthesis and spinal stenosis.