The role of cytokine receptor-like factor 1 (CRLF1) in facet joint osteoarthritis pathogenesis.

BACKGROUND: Facet joint osteoarthritis (FJOA) is a prevalent condition contributing to low back pain, particularly in the elderly population. This study aimed to investigate the potential role of Cytokine Receptor-like Factor 1 (CRLF1) in FJOA pathogenesis and its therapeutic implications. METHODS: Bioinformatics analysis was utilized to identify CRLF1 as the target gene, followed by quantification of CRLF1 expression levels and joint degeneration degree using immunohistochemistry (IHC). In primary chondrocytes, the inhibition of CRLF1 expression by siRNA was performed, and Western blot analysis was conducted to evaluate the involvement of the extracellular matrix and MAPK/ERK signaling pathway. Flow cytometry was employed to assess the apoptosis rate of chondrocytes, while immunofluorescence (IF) was utilized to evaluate the localization of CRLF1, cleaved-caspase3, MMP13, COL2A1, and ERK. RESULTS: The expression of CRLF1 was found to be significantly elevated in FJOA tissues compared to normal tissues. Through the use of loss-of-function assays, it was determined that CRLF1 not only enhanced the rate of apoptosis in chondrocytes, but also facilitated the degradation of the extracellular matrix in vitro. Furthermore, CRLF1 was found to activate the ERK1/2 pathways. The pro-arthritic effects elicited by CRLF1 were mitigated by treatment with the MEK inhibitor U0126 in chondrocytes. CONCLUSION: These results suggest that CRLF1 enhances chondrocytes apoptosis and extracellular matrix degration in FJOA and thus may therefore be a potential therapeutic target for FJOA.

Bushen Huoxue decotion-containing serum prevents chondrocyte pyroptosis in a m6A-dependent manner in facet joint osteoarthritis.

BACKGROUND: Facet joint osteoarthritis (FJOA) is a common lumbar osteoarthritis characterized by degeneration of small joint cartilage. Bushen Huoxue decotion (BSHXD) has good therapeutic effects on OA. Our work aimed to further probe the pharmacological effects of BSHXD-containing serum (BSHXD-CS) on FJOA and define underlying the mechanisms invovled. METHODS: To establish a FJOA cell model, primary rat chondrocytes were treated with LPS. The mRNA and protein expressions were assessed using qRT-PCR and western blot, respectively. The secretion levels of pro-inflammatory cytokines were measured by ELISA. Cell viability was determined by CCK8 assay. The global m6A level was detected by the kit, and NLRP3 mRNA m6A level was determined by Me-RIP assay. The molecular interactions were analyzed by RIP and RNA pull-down assays. RESULTS: BSHXD-CS treatment relieved LPS-induced cell injury, inflammation, NLRP3 inflammasome and pyroptosis in chondrocytes (all p < 0.05). LPS-induced NLRP3 upregulation in chondrocytes was related to its high m6A modification level (p < 0.05). It was also observed that BSHXD-CS reduced LPS-induced m6A modification in chondrocytes via repressing STAT3 (all p < 0.05), suggesting BSHXD-CS could repress NLRP3 expression via m6A-dependent manner. Moreover, DAA, a m6A specific inhibitor, was proved to strengthen the protectively roles of BSHXD-CS on LPS-challenged pytoptosis (all p < 0.05). CONCLUSION: BSHXD-CS inhibited NLRP3 inflammasome activation and pyroptosis in chondrocytes to repress OA progression by reducing RNA m6A modification.

Relationship between facet joint osteoarthritis and lumbar paraspinal muscle atrophy: a cross-sectional study.

OBJECTIVE: The paraspinal muscles play an essential role in the stabilization of the lumbar spine. Lumbar paraspinal muscle atrophy has been linked to chronic back pain and degenerative processes within the spinal motion segment. However, the relationship between the different paraspinal muscle groups and facet joint osteoarthritis (FJOA) has not been fully explored. METHODS: In this cross-sectional study, the authors analyzed adult patients who underwent lumbar spinal surgery between December 2014 and March 2023 for degenerative spinal conditions and had preoperative MRI and CT scans. The fatty infiltration (FI) and functional cross-sectional area (fCSA) of the psoas, erector spinae, and multifidus muscles were assessed on axial T2-weighted MR images at the level of the upper endplate of L4 based on established studies and calculated using custom-made software. Intervertebral disc degeneration at each lumbar level was evaluated using the Pfirrmann grading system. The grades from each level were summed to report the cumulative lumbar Pfirrmann grade. Weishaupt classification (0-3) was used to assess FJOA at all lumbar levels (L1 to S1) on preoperative CT scans. The total lumbar FJOA score was determined by adding the Weishaupt grades of both sides at all 5 levels. Correlation and linear regression analyses were conducted to assess the relationship between FJOA and paraspinal muscle parameters. RESULTS: A total of 225 patients (49.7% female) with a median age of 61 (IQR 54-70) years and a median BMI of 28.3 (IQR 25.1-33.1) kg/m2 were included. After adjustment for age, sex, BMI, and the cumulative lumbar Pfirrmann grade, only multifidus muscle fCSA (estimate -4.69, 95% CI -6.91 to -2.46; p < 0.001) and FI (estimate 0.64, 95% CI 0.33-0.94; p < 0.001) were independently predicted by the total FJOA score. A similar relation was seen with individual Weishaupt grades of each lumbar level after controlling for age, sex, BMI, and the Pfirrmann grade of the corresponding level. CONCLUSIONS: Atrophy of the multifidus muscle is significantly associated with FJOA in the lumbar spine. The absence of such correlation for the erector spinae and psoas muscles highlights the unique link between multifidus muscle quality and the degeneration of the spinal motion segment. Further research is necessary to establish the causal link and the clinical implications of these findings.

Inflammation in the posterior elements, in particular the facet joint and facet joint ankylosis over 2-year follow-up in radiographic axial spondyloarthritis.

OBJECTIVES: To assess the association of posterior element (PE) and facet joint (FJ) inflammation with subsequent new FJ ankylosis (FJA) on MRI, in patients with radiographic axial spondyloarthritis (r-axSpA). METHODS: Patients from the Sensitive Imaging in Ankylosing Spondylitis cohort, inclusion criteria r-axSpA and ≥1 radiographic spinal syndesmophyte, were studied. MRI of the full spinal was performed at baseline, 1 and 2 years. PE/FJ inflammatory lesions and FJA were assessed per vertebral unit (VU) level by three readers. With multilevel time-lagged autoregressive generalised estimated equations, the association between PE/FJ inflammation and the subsequent development of FJA was investigated, taking the reader and VU levels into account. RESULTS: Out of the 58 patients with at least 2 reader scores available, mean age 49 (SD 10) years, 84% men, 59% had baseline PE inflammation, 24% had FJ inflammation and 26% had FJA. PE inflammation was more prevalent in the lower thoracic spine and FJ inflammation in the upper thoracic spine. VU with PE or FJ inflammation showed subsequent new FJA in two and one VU levels, respectively. The probability of developing FJA doubled with prior FJ inflammation. In multilevel analysis, FJ inflammation was associated with subsequent FJA (OR=3.8, 95% CI: 1.5 to 9.8), while no association was found between PE inflammation and new FJA (OR=1.2 (0.6-2.4)). CONCLUSIONS: FJ inflammation is rare in severe r-axSpA, but when present, the likelihood of developing subsequent FJA is over three times higher compared with FJ without inflammation. This finding contributes to the understanding of the relationship between inflammation and ankylosis at the same anatomical location in patients with axSpA.

Asymmetrical atrophy of the paraspinal muscles in patients undergoing unilateral lumbar medial branch radiofrequency neurotomy.

ABSTRACT: Lumbar medial branch radiofrequency neurotomy (RFN), a common treatment for chronic low back pain due to facet joint osteoarthritis (FJOA), may amplify paraspinal muscle atrophy due to denervation. This study aimed to investigate the asymmetry of paraspinal muscle morphology change in patients undergoing unilateral lumbar medial branch RFN. Data from patients who underwent RFN between March 2016 and October 2021 were retrospectively analyzed. Lumbar foramina stenosis (LFS), FJOA, and fatty infiltration (FI) functional cross-sectional area (fCSA) of the paraspinal muscles were assessed on preinterventional and minimum 2-year postinterventional MRI. Wilcoxon signed-rank tests compared measurements between sides. A total of 51 levels of 24 patients were included in the analysis, with 102 sides compared. Baseline MRI measurements did not differ significantly between the RFN side and the contralateral side. The RFN side had a higher increase in multifidus FI (+4.2% [0.3-7.8] vs +2.0% [-2.2 to 6.2], P = 0.005) and a higher decrease in multifidus fCSA (-60.9 mm 2 [-116.0 to 10.8] vs -19.6 mm 2 [-80.3 to 44.8], P = 0.003) compared with the contralateral side. The change in erector spinae FI and fCSA did not differ between sides. The RFN side had a higher increase in multifidus muscle atrophy compared with the contralateral side. The absence of significant preinterventional degenerative asymmetry and the specificity of the effect to the multifidus muscle suggest a link to RFN. These findings highlight the importance of considering the long-term effects of lumbar medial branch RFN on paraspinal muscle health.

A possible correlation between facet orientation and development of degenerative cervical spinal stenosis.

BACKGROUND: Previous studies have demonstrated the relationship between sagittal facet orientation and cervical degenerative spondylolisthesis. However, the associations between facet orientation and cervical spinal stenosis (CSS) have rarely been studied. METHODS: One hundred twenty patients with CSS (CSS group) and 120 healthy participants (control group) were consecutively enrolled. The cervical facet angles and anteroposterior diameter (A-P diameter) of spinal canal at each subaxial cervical levels were measured using axial magnetic resonance imaging. The intersection angle of the midsagittal line of the vertebra to the facet line represents the orientation of the facet joint. RESULTS: The facet angles on the right side at C2- C3 and C3-C4 in CSS group and at C2- C3 in control group had significantly higher values than those of the other sides. Besides, the facet angles and A-P diameter of spinal canal in CSS group were significantly smaller than those in control group at all levels (p < 0.05). CONCLUSIONS: Our study demonstrated that patients with CSS have smaller axial cervical facet joint angles compared to the healthy individuals. Further studies are needed to elicit the specific underlying mechanism between sagittalization of the cervical facet joints and the pathology of CSS.

Surgical versus nonsurgical management of lumbar degenerative spondylolisthesis based on spinal canal cross-sectional area.

Disability and pain associated with lumbar degenerative spondylolisthesis (LDS) result in a significant burden on both the healthcare costs and patients' quality of life. Currently, there exists controversy regarding employment of either nonsurgical management (NSM) or surgical management (SM) in a clinical setting. Spinal canal cross-sectional area (SCA) has been an important morphological parameter for the analysis of LDS. However, there is lack of research about the comparative value of NSM and SM according to SCA. Moreover, previous research have not yet evaluated the clinical most suitable cutoff values of SCA. The objective of this research was to evaluate the effective of NSM and SM for LDS using SCA as an objective morphological parameter. The axial T2 magnetic resonance imaging images were obtained from each patient. We collected SCA samples from 149 patients with LDS. 72 patients underwent SM and the rest did NSM. We measured SCA at the L4/5 LDS on magnetic resonance imaging using a picture archiving and communications system. We measured SCA at the intervertebral disk posterior border, turning down to reach the facet joint side on the opposite edge at the L4/5 level. The average SCA value was 114.34 ±â€…48.11 mm2 in the NSM group and 69.88 ±â€…27.87 mm2 in the SM group. Therefore, the SM group had considerably lower SCA (P < .001). In view of the effectiveness of SCA as a prediction factor of surgical option, Receiver Operating Characteristic curve analysis show the optimal cutoff value for SCA as 83.21 mm2, with 70.8% sensitivity, 71.4% specificity, and an area under the curve of 0.80 (95% CI, 0.73-0.87). The narrower the SCA, the higher the probability of SM. Thus, it is proposed that to evaluate surgical decision making, the pain physician should carefully inspect the SCA.

Reporting of Facet Joint Inflammation in Lumbar Spine MRI Studies in Patients With Low Back Pain.

STUDY DESIGN: Retrospective. OBJECTIVE: We aimed to assess the frequency of facet joint inflammatory features noted in routine radiology reports of lumbar spine magnetic resonance imaging (MRI) studies among patients with chronic low back pain. SUMMARY OF BACKGROUND DATA: Facet joint arthropathy is one of the most common causes of chronic low back pain. It may encompass various inflammatory imaging characteristics, such as facet joint effusion, bone marrow edema, and soft tissue edema. The extent to which radiology reports mention inflammatory features of the lumbar facet joints and the accuracy of these reports have not been investigated. MATERIALS AND METHODS: The authors performed a chart review on 49 subjects with previous facet-related interventions ( i.e . medial branch blocks or intra-articular facet joint injection) and MRI available in the medical record. One senior musculoskeletal radiologist and a musculoskeletal radiology fellow graded the inflammatory features using a published facet joint inflammation grading system [Gold Standard (GS)]. The authors identified the inflammatory markers mentioned in the radiology reports and calculated the sensitivity and positive predictive value of the radiology reports compared with GS readings. RESULTS: Compared with the GS, the sensitivity of radiology reports for facet joint effusion, bone marrow, and soft tissue edema ranged from 6% to 22%, and the positive predictive value ranged from 25% to 100%. L4/5 had the highest number of cases with inflammatory features noted on the reports. CONCLUSION: Inflammatory findings, such as facet joint effusion, bone marrow edema, and soft tissue edema, are not commonly identified in radiology reports. Further investigations are needed to determine the clinical importance of MRI-detected lumbar facet joint inflammatory features as a potential mechanism of nociception and as a predictor of outcomes following injections or other therapies.

Facet joint tropism, pelvic incidence and intervertebral height index: associations with facet joint osteoarthritis in lumbar spinal stenosis.

BACKGROUND CONTEXT: Facet joint osteoarthritis (FJOA) is associated with lumbar disc degeneration and has a significant role in the development of lumbar spinal stenosis (LSS). The relationship between various radiographic parameters and the grade of FJOA is not well understood. PURPOSE: To explore radiographical parameters associated with FJOA in LSS without lumbar dynamic instability. STUDY DESIGN: Retrospective study analysis. PATIENT SAMPLE: A total of 122 patients diagnosed with LSS who visited our hospital between January 2015 and July 2022. OUTCOME MEASURES: We evaluated radiographic parameters of patients at L4-5 including lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), grades of FJOA, facet joint orientation (FO), facet joint tropism (FT), intervertebral height index (IHI) and the relative cross-sectional area (RCSA) of paraspinal muscles. METHODS: Patients diagnosed with LSS between January 2015 and July 2022 were enrolled. Demographic characteristics and radiographic parameters were collected. Spinopelvic parameters were measured through the preoperative lateral image of the whole spine, including LL, PI, pelvic tilt, and sacral slope. Lumbar computed tomography scan and magnetic resonance imaging were collected to measure the FO, FT, IHI, and the RCSA of paraspinal muscles respectively. Patients were divided into three groups according to the severity of FJOA graded by the Weishaupt classification: grade 0 and grade 1 were group A, grade 2 were group B, and grade 3 were group C. All variables were compared among the three groups, while the relationship between parameters and grades of FJOA were also analyzed. RESULTS: A total of 122 patients were included. PI was significantly greater in group C compared to group A (p = 0.025) and group B (p=0.022). FT was significantly greater in group C compared to group A (p<.001) and group B (p<.001). The RCSA of multifidus in group A were significantly greater than that in group B (p=0.02) and C (p=0.002). Additionally, FO in group C were significantly lower than group A (p<.001) and group B (p=0.028). The IHI in group C was significantly lower than group A (p=0.017). The correlation analysis indicated that grades of FJOA was positively related to Age, BMI (body mass index), PI, LL and FT, while negatively related to IHI, FO, RCSA of multifidus and RCSA of psoas major. Furthermore, the logistics regression showed that FT, PI, and IHI were important influence factors for FJOA. CONCLUSIONS: The current study confirmed that FT, PI and IHI were significantly associated with grades of FJOA at L4-5. Additionally, longitudinal studies are needed to understand the causal relationship between these parameters and FJOA.

Comprehensive Grading System of Inflammatory Features of the Lumbar Facet Joints on Magnetic Resonance Imaging.

STUDY DESIGN: Retrospective. OBJECTIVE: We aimed to describe a magnetic resonance imaging (MRI)-based grading system of inflammatory features of the lumbar facet joints using an atlas and assess its reliability. SUMMARY OF BACKGROUND DATA: Chronic low back pain is often caused by facet joint arthropathy. Inflammatory features are often evident on MRI. While several grading systems of facet arthropathy have been described, there is scant data on the reliability of these systems, and none focus exclusively on inflammatory features. MATERIALS AND METHODS: We describe a grading system that assesses facet joint effusion, bone marrow edema, and soft tissue edema. Each feature was graded from 0 to 3 (facet edema) or 0 to 2 (bone marrow edema intensity and extent, soft tissue edema intensity and extent). Four spine experts graded MRIs of 50 subjects at the bilateral L3/4, L4/5, and L5/S1 levels. All subjects had symptomatic facet arthropathy and received therapeutic facet joint injections. We assessed the intra-reader and inter-reader reliability of each feature at each joint and summarized across all six joints. RESULTS: The mean age of subjects was 56 years (SD = 17), and 48% were female. The injections occurred at the L3/4 level in 12% of cases, at L4/5 in 88%, and at L5/S1 in 80% of cases. The intra-reader reliability kappa's for each feature ranged from 0.42 to 0.81. In contrast, the inter-reader reliability kappa values for each feature ranged from 0.37 to 0.54. CONCLUSION: MRI inflammatory features of the lumbar facet joints are often noted in patients with low back pain. The proposed grading system is reliable and could serve as a research tool for studies assessing the clinical relevance and prognostic value of these features.

The effect of integrative Korean medicine treatment on symptomatic lumbar facet joint cysts: A case series.

OBJECTIVE: The optimal treatment for facet joint cysts (FJCs) has remained controversial. Despite a higher success rate than the conservative option, surgical treatments may pose risks of postoperative complications and comorbidities may make the surgical approach difficult. Thus, this study reports four cases of pain amelioration and resorption of FJCs through noninvasive integrative Korean Medicine treatment. METHODS: For intervention, four patients with symptomatic FJCs underwent integrative Korean medicine treatment with acupuncture, herbal medicine, pharmacopuncture, and Chuna manual therapy; after completion of the series of treatment sessions, patients were re-examined with magnetic resonance imaging (MRI). RESULTS: Pain disappeared within 2 months for all four patients; the amelioration of pain was sustained for more than 6 months. Furthermore, the disappearance of FJCs was confirmed by MRI after a certain period from the time of pain disappearance. CONCLUSIONS: This study reported the effectiveness of non-invasive, integrative Korean medicine treatment for patients with FJCs; this method shows promise as a conservative treatment option for patients with FJCs.

Decreased FoxO1 expression contributes to facet joint osteoarthritis pathogenesis by impairing chondrocyte migration and extracellular matrix synthesis.

Facet joint osteoarthritis (FJOA), a condition commonly observed in individuals of middle to old age, has been relatively under-researched compared to other subtypes of osteoarthritis (OA). This study investigated the role of transcription factor FoxO1 in FJOA using a Col2a1-creERT knock-in mouse model. It was found that FoxO1 deletion led to severe osteoarthritic changes, indicating that FoxO1 played a critical role in cartilage homeostasis. Transcriptome sequencing was performed on degenerated cartilage from FoxO1-deleted mice. This process identified differentially expressed genes (DEGs), offering insights into the molecular mechanisms underlying FJOA. Bioinformatics analysis, including Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA) and protein-protein interaction (PPI) network analysis, identified Itgb3, Itga1, Itga6, Itga7, Itga8, Itga10, Col1a1, and Il6, as potential key contributors to FJOA after FoxO1 deletion. Importantly, overexpression of Itgb3 and inhibition of Il6 counteracted FoxO1 knockdown-induced impairments in chondrocyte migration and extracellular matrix synthesis, respectively. This study discovered FoxO1 as a key regulator of the pathogenesis of FJOA, helped unravel the complex molecular mechanisms underlying FJOA, and contributed to the development of promising therapeutic avenues toward FJOA.

CT-guided lumbar facet cyst rupture and corticosteroid injection: technique, approach, and procedural and clinical success rates.

PURPOSE: To evaluate success rates of computed tomography (CT)-guided lumbar facet synovial cyst (LFC) rupture. MATERIALS AND METHODS: We retrospectively reviewed all LFC ruptures performed by a single musculoskeletal radiologist with > 10 years of experience, using posterior facet approach and/or direct puncture by ipsilateral/contralateral interlaminar, or transforaminal approach. All patients also received a corticosteroid injection. Rupture rates were calculated, and clinical success rate was determined through medical record review. Pre-procedure magnetic resonance imaging (MRI) images and CT procedure images were also reviewed for LFC and facet joint imaging features that may predict rupture. RESULTS: There were 37 patients, 17 (46%) female and 20 (54%) male, ages 62 ± 12 (range 39-87) years. Thirty-four (92%) of LFC were successfully ruptured, 17 (50%) by facet approach and 17 (50%) by direct cyst puncture. At least one direct puncture approach was possible in 35 (95%) patients. No MRI or CT LFC or facet joint features predicted cyst rupture. Thirty-one (91%) of patients reported immediate pain relief, and 19 (53%) did not have further intervention for LFC-related pain. Sixteen (84%) of these patients remained pain-free for an average follow-up time period of 28 months. Fourteen (39%) of patients required surgical intervention. There were no complications. CONCLUSION: Our systematic approach to CT-guided LFC rupture is safe and has high technical and clinical success rates similar to prior studies. Since there are no definitive imaging features that determine rupture success, this procedure can almost always be attempted as a first-line treatment for LFC.

Semiautomatic Assessment of Facet Tropism From Lumbar Spine MRI Using Deep Learning: A Northern Finland Birth Cohort Study.

STUDY DESIGN: This is a retrospective, cross-sectional, population-based study that automatically measured the facet joint (FJ) angles from T2-weighted axial magnetic resonance imagings (MRIs) of the lumbar spine using deep learning (DL). OBJECTIVE: This work aimed to introduce a semiautomatic framework that measures the FJ angles using DL and study facet tropism (FT) in a large Finnish population-based cohort. SUMMARY OF DATA: T2-weighted axial MRIs of the lumbar spine (L3/4 through L5/S1) for (n=1288) in the NFBC1966 Finnish population-based cohort were used for this study. MATERIALS AND METHODS: A DL model was developed and trained on 430 participants' MRI images. The authors computed FJ angles from the model's prediction for each level, that is, L3/4 through L5/S1, for the male and female subgroups. Inter-rater and intrarater reliability was analyzed for 60 participants using annotations made by two radiologists and a musculoskeletal researcher. With the developed method, we examined FT in the entire NFBC1966 cohort, adopting the literature definitions of FT thresholds at 7° and 10°. The rater agreement was evaluated both for the annotations and the FJ angles computed based on the annotations. FJ asymmetry ( - was used to evaluate the agreement and correlation between the raters. Bland-Altman analysis was used to assess the agreement and systemic bias in the FJ asymmetry. The authors used the Dice score as the metric to compare the annotations between the raters. The authors evaluated the model predictions on the independent test set and compared them against the ground truth annotations. RESULTS: This model scored Dice (92.7±0.1) and intersection over union (87.1±0.2) aggregated across all the regions of interest, that is, vertebral body (VB), FJs, and posterior arch (PA). The mean FJ angles measured for the male and female subgroups were in agreement with the literature findings. Intrarater reliability was high, with a Dice score of VB (97.3), FJ (82.5), and PA (90.3). The inter-rater reliability was better between the radiologists with a Dice score of VB (96.4), FJ (75.5), and PA (85.8) than between the radiologists and the musculoskeletal researcher. The prevalence of FT was higher in the male subgroup, with L4/5 found to be the most affected region. CONCLUSION: The authors developed a DL-based framework that enabled us to study FT in a large cohort. Using the proposed method, the authors present the prevalence of FT in a Finnish population-based cohort.

3D zero-echo time and 3D T1-weighted gradient-echo MRI sequences as an alternative to CT for the evaluation of the lumbar facet joints and lumbosacral transitional vertebrae.

BACKGROUND: Computed tomography (CT) is the reference standard for assessment of the bone. Magnetic resonance imaging (MRI) developments enable a CT-like visualization of the osseous structures. PURPOSE: To assess the diagnostic performance of 3D zero-echo time (3D-ZTE) and 3D T1-weighted gradient-echo (3D-T1GRE) MRI sequences for the evaluation of lumbar facet joints (LFJs) and the detection of lumbosacral transitional vertebrae (LSTV) using CT as the reference standard. MATERIAL AND METHODS: In total, 87 adult patients were included in this prospective study. Evaluation of degenerative changes of the facet joints at the L3/L4, L4/L5, and L5/S1 levels on both sides was performed by two readers using a 4-point Likert scale. LSTV were classified according to Castelvi et al. Image quality was quantitatively measured using the signal-to-noise (SNR) and contrast-to-noise (CNR) ratios. Intra-reader, inter-reader, and inter-modality reliability were calculated using Cohen's kappa statistic. RESULTS: Intra-reader agreement for 3D-ZTE, 3D-T1GRE, and CT was 0.607, 0.751, and 0.856 and inter-reader agreement was 0.535, 0.563, and 0.599, respectively. The inter-modality agreement between 3D-ZTE and CT was 0.631 and between 3D-T1GRE and CT 0.665. A total of LSTV were identified in both MR sequences with overall comparable accuracy compared to CT. Mean SNR for bone, muscle, and fat was highest for 3D-T1GRE and mean CNR was highest for CT. CONCLUSION: 3D-ZTE and 3D-T1GRE MRI sequences can assess the LFJs and LSTV and may serve as potential alternatives to CT.

Endplate and Facet Joint Changes in Cervical Spondylotic Myelopathy.

BACKGROUND: Modic changes (MC) of the vertebral endplates and facet joint degeneration are common causes of neck pain. No previous study has shown the prevalence of and relationship between MC and facet joint changes in cervical spondylotic myelopathy (CSM). The objective of this article was to study the endplate and facet joint changes in CSM. METHODS: Magnetic resonance imaging of the cervical spine in 103 patients with CSM was retrospectively evaluated. The scans were evaluated by 2 raters, who classified spinal segments according to the Modic classification and the degree of facet degeneration. RESULTS: In patients <50 years old, there were no MC in 61.5%. In patients with MC, Modic type II at C4-C5 was observed most frequently. MC were found in 71.4% of patients ≥50 years old. In patients with MC, Modic type II at C3-C4 was observed most frequently. Degenerative changes of the facet joints were found frequently in both patients <50 years old (77.5%) and patients ≥50 years (90.2%), and grade I degeneration was observed most frequently in both groups. There was a significant correlation between MC and facet joint changes. CONCLUSIONS: MC in the cervical spine are common magnetic resonance imaging findings in patients with CSM ≥50 years old. Degenerative facet joint changes are found in the majority of patients with CSM regardless of age. We found a significant correlation between MC and facet joint changes at the same level, indicating that both imaging findings are involved in a common pathophysiological pathway.

Grading Systems of Lumbar Facet Joint Inflammatory Changes on Magnetic Resonance Imaging: A Scoping Review.

STUDY DESIGN: A scoping review. OBJECTIVE: We aimed to identify and characterize grading systems of the inflammatory features of the lumbar facet joints (FJs) noted on magnetic resonance imaging and summarize their reliability. SUMMARY OF BACKGROUND DATA: Chronic low back pain is one of the most common causes of disability worldwide and is frequently accompanied by FJ osteoarthritis. Inflammatory changes in the lumbar FJs are commonly noted in imaging studies of patients with FJ osteoarthritis and low back pain. Several grading systems for these inflammatory changes have been developed. However, these grading system's features and reliability have yet to be reviewed. MATERIALS AND METHODS: We performed a literature search of studies reporting grading systems for FJ inflammatory changes published in English or Spanish between 1985 and 2022. We collected data on reported interreader reliability measures of each grading system. Finally, we compared the features of inflammation described by each system. RESULTS: Six studies met the inclusion criteria and were used in our analysis. Features commonly graded in these systems are the hyperintensity signal noted within the FJ, bone marrow edema, and the extent of the soft-tissue edema surrounding the FJs. We found that the interreader reliability measures ranged from 0.56 to 0.96. CONCLUSIONS: Only 6 studies have reported methods for documenting inflammation in the FJs. Studies varied in the precise tissues and phenomena included in the grading systems. However, the systems were generally reliable. Future studies should document the reliability of these methods when independent investigators are not involved in developing the classification schemes. Further work might combine one or more of these measures to establish a standard and reliable grading system for inflammatory changes in the FJs, including signal intensity within the joint, bone marrow edema, and soft-tissue inflammation.

MiR-337-3p confers protective effect on facet joint osteoarthritis by targeting SKP2 to inhibit DUSP1 ubiquitination and inactivate MAPK pathway.

OBJECTIVE: To probe the performance of miR-337-3p on the facet joint osteoarthritis (FJOA) and its underlying mechanism. METHODS: qRT-PCR and Western blot were utilized to analyze the levels of miR-337-3p and DUSP1 in the synovial tissues from 36 FJOA patients and 10 healthy controls. The human synovial fibroblasts of FJOA were isolated and cultured followed by cell transfection. Then, cells were exposed to 10 ng/mL of IL-1ß to induce inflammatory response of synovial fibroblasts. The alternation on cell biological function in cell models was determined. The binding of miR-337-3p and SKP2 was predicted by StarBase, TargetScan, DIANA-microT and miRmap, and further verified by RIP assay and dual-luciferase reporter assay. Co-IP experiment and ubiquitination assay were used to display the binding of SKP2 and DUSP1 as well as the ubiquitination and degradation of DUSP1. After that, the FJOA rat model was established and miR-337-3p mimic or negative control was given to rats by tail vein injection. The pathological changes of synovial tissues, synovitis score, and inflammation level in rats were assessed. RESULTS: The low expressions of miR-337-3p and DUSP1 were noticed in the synovial tissues of FJOA patients and in IL-1ß-induced synovial fibroblasts, and highly expressed p-p38 MAPK was noticed. Upregulation of miR-337-3p/DUSP1 or downregulation of SKP2 inhibited IL-1ß-induced proliferation and inflammatory response of synovial fibroblasts. SKP2 was the target gene of miR-337-3p, and SKP2 induced the ubiquitination and degradation of DUSP1. MiR-337-3p exerted a protective effect on FJOA rats by alleviating damage of rat synovial tissues, promoting cell apoptosis and repressing inflammatory response. CONCLUSION: MiR-337-3p plays a protective role in FJOA by negatively targeting SKP2 to suppress DUSP1 ubiquitination and inactivate the p38 MAPK pathway.

Level dependent alterations in human facet cartilage mechanics and bone morphometry with spine degeneration.

The zygapophyseal joints of the spine, also known as the facet joints, are paired diarthrodial joints posterior to the intervertebral disc and neural elements. The pathophysiology of facet osteoarthritis (OA), as well as crosstalk between the disc and facets, remains largely understudied compared to disc degeneration. The purpose of this study was to characterize alterations to human facet cartilage and subchondral bone across a spectrum of degeneration and to investigate correlations between disc and facet degeneration. Human lumbar facet articular surfaces from six independent donors were subject to creep indentation mechanical testing to quantify cartilage mechanical properties, followed by microcomputed tomography (µCT) analyses for subchondral bone morphometry. The degenerative state of each articular surface was assessed via macroscopic scoring and via Osteoarthritis Research Society International histopathology scoring. Our data suggest reduced facet cartilage compressive and tensile moduli and increased permeability with increasing degenerative grade, particularly at the lower levels of the spine. µCT analyses revealed spinal level-dependent alterations to the subchondral bone, with an increase in trabecular bone at the L4-L5 level, but a decrease at the upper levels of the lumbar spine with increasing degenerative grade. Cortical bone volume fraction was generally decreased with increasing degenerative grade across spinal levels. Correlation analysis revealed several associations between quantitative measures of disc degeneration and facet OA. This study showed that alterations in the mechanical properties of facet cartilage and in the structural properties of facet subchondral bone correlated with aspects of disc degeneration and were highly dependent on spinal level.

The Lumbar Facet Capsular Ligament Becomes More Anisotropic and the Fibers Become Stiffer With Intervertebral Disc and Facet Joint Degeneration.

Degeneration of the lumbar spine, and especially how that degeneration may lead to pain, remains poorly understood. In particular, the mechanics of the facet capsular ligament may contribute to low back pain, but the mechanical changes that occur in this ligament with spinal degeneration are unknown. Additionally, the highly nonlinear, heterogeneous, and anisotropic nature of the facet capsular ligament makes understanding mechanical changes more difficult. Clinically, magnetic resonance imaging (MRI)-based signs of degeneration in the facet joint and the intervertebral disc (IVD) correlate. Therefore, this study examined how the nonlinear, heterogeneous mechanics of the facet capsular ligament change with degeneration of the lumbar spine as characterized using MRI. Cadaveric human spines were imaged via MRI, and the L2-L5 facet joints and IVDs were scored using the Fujiwara and Pfirrmann grading systems. Then, the facet capsular ligament was isolated and biaxially loaded. The nonlinear mechanical properties of the ligament were obtained using a nonlinear generalized anisotropic inverse mechanics analysis (nGAIM). Then a Holzapfel-Gasser-Ogden (HGO) model was fit to the stress-strain data obtained from nGAIM. The facet capsular ligament is stiffer and more anisotropic at larger Pfirrmann grades and higher Fujiwara scores than at lower grades and scores. Analysis of ligament heterogeneity showed all tissues are highly heterogeneous, but no distinct spatial patterns of heterogeneity were found. These results show that degeneration of the lumbar spine including the facet capsular ligament appears to be occurring as a whole joint phenomenon and advance our understanding of lumbar spine degeneration.