Lumbar Facet Joint Osteoarthritis Research Articles

Hypoxia-treated adipose mesenchymal stem cell-derived exosomes attenuate lumbar facet joint osteoarthritis

BackgroundLumbar facet joint osteoarthritis (LFJ OA) is a common disease, and there is still a lack of effective disease-modifying therapies. Our aim was to determine the therapeutic effect of hypoxia-treated adipose mesenchymal stem cell (ADSC)-derived exosomes (Hypo-ADSC-Exos) on the protective effect against LFJ OA.MethodsThe protective effect of Hypo-ADSC-Exos against LFJ OA was examined in lumbar spinal instability (LSI)-induced LFJ OA models. Spinal pain behavioural assessments and CGRP (Calcitonin Gene-Related Peptide positive) immunofluorescence were evaluated. Cartilage degradation and subchondral bone remodelling were assessed by histological methods, immunohistochemistry, synchrotron radiation-Fourier transform infrared spectroscopy (SR-FTIR), and 3D X-ray microscope scanning.ResultsHypoxia enhanced the protective effect of ADSC-Exos on LFJ OA. Specifically, tail vein injection of Hypo-ADSC-Exos protected articular cartilage from degradation, as demonstrated by lower FJ OA scores of articular cartilage and less proteoglycan loss in lumbar facet joint (LFJ) cartilage than in the ADSC-Exo group, and these parameters were significantly improved compared to those in the PBS group. In addition, the levels and distribution of collagen and proteoglycan in LFJ cartilage were increased in the Hypo-ADSC-Exo group compared to the ADSC-Exo or PBS group by SR-FTIR. Furthermore, Hypo-ADSC-Exos normalized uncoupled bone remodelling and aberrant H-type vessel formation in subchondral bone and effectively reduced symptomatic spinal pain caused by LFJ OA in mice compared with those in the ADSC-Exo or PBS group.ConclusionsOur results show that hypoxia is an effective method to improve the therapeutic effect of ADSC-Exos on ameliorating spinal pain and LFJ OA progression.

Relationship between lumbar facet joint osteoarthritis and comorbidities: A cross-sectional study in the Japanese community

BackgroundFew epidemiological studies have evaluated associations between lumbar facet joint (LFJ) osteoarthritis (OA) and comorbidities. This study aimed to investigate the prevalence of LFJ OA in a Japanese community population and associations between LFJ OA and underlying diseases, including lower extremity OA. MethodsThis epidemiological cross-sectional study evaluated LFJ OA in 225 Japanese community residents (81 males, 144 females; median age, 66 years) using magnetic resonance imaging (MRI). LFJ OA from L1–L2 to L5–S1 was evaluated using a 4-grade classification. Associations between LFJ OA and comorbidities were examined using multiple logistic regression analyses adjusting for age, sex, and body mass index. ResultsPrevalences of LFJ OA were 28.6% at L1–L2, 36.4% at L2–L3, 48.0% at L3–L4, 57.3% at L4–L5, and 44.2% at L5–S1. Males were significantly more likely to have LFJ OA at several spinal levels (L1–L2 45.7% vs 18.9%, p < 0.001; L2–L3 46.9% vs 30.6%, p < 0.05; L4–L5 67.9% vs 51.4%, p < 0.05). LFJ OA was present in 50.0% of residents <50 years old, 68.4% at 50–59 years old, 86.3% at 60–69 years old, and 85.1% at ≥70 years old. Multiple logistic regression analysis showed no associations between LFJ OA and comorbidities. ConclusionsThe prevalence of LFJ OA as evaluated by MRI was >85% at ≥60 years old and highest at the L4–L5 spinal level. Males were significantly more likely to have LFJ OA at several spinal levels. Comorbidities were not associated with LFJ OA.

Comprehensive analysis of microRNA expression in lumbar facet joint capsules and synovium of patients with osteoarthritis: Comparison between early-stage and late-stage osteoarthritis samples from a single individual

BackgroundMicroRNA is attracting attention as a therapeutic target for osteoarthritis. We focused on joint capsules and synovium in lumbar facet joint osteoarthritis. The purpose of this study was to identify microRNAs that are upregulated in lumbar facet joint capsules and synovium with osteoarthritis. MethodsWe included patients who underwent spinal fusion for degenerative lumbar spine diseases. We selected patients who had both early-stage and late-stage facet joint osteoarthritis in a single individual. We extracted joint capsule and synovium samples from these patients and isolated microRNAs. During the screening phase, we compared early-stage and late-stage osteoarthritis samples from the same individual. We identified microRNAs with >2-fold change in expression in 75% or more of patients with late-stage osteoarthritis using next generation sequencing. During the technical validation phase, the same samples were used for real-time polymerase chain reaction. We identified microRNAs with >2-fold change in expression in 62.5% or more of patients with late-stage osteoarthritis. ResultsOf 40 patients who underwent spinal fusion, we selected eight patients with both early-stage and late-stage facet joint osteoarthritis. During the screening phase, we identified eight upregulated microRNAs out of 2274 microRNAs in late-stage OA. In late-stage OA, two microRNAs (miR-133a-5p and miR-144-3p) were upregulated in seven patients and six microRNAs (miR-133a-3p, miR-133b, miR-206, miR-20a-5p, miR-301a-3p, and miR-32-5p) were upregulated in six patients. During the technical validation phase, we found significant upregulation of miR-144-3p expression in late-stage osteoarthritis compared with early-stage osteoarthritis. Expression of the other microRNAs was not significantly different according to the paired-t test. However, miR-133a-3p, miR-133b, and miR-206 were upregulated >2-fold in 62.5% or more of patients with late-stage osteoarthritis. ConclusionsSome of the microRNAs identified in this study might be involved in joint capsule degeneration or synovitis.

Risk Factors for Poor Outcomes Following Minimally Invasive Discectomy: A Post Hoc Subgroup Analysis of 2-Year Follow-up Prospective Data.

ObjectiveA post hoc subgroup analysis of prospectively collected data from a randomized controlled trial was conducted to identify risk factors related to poor outcomes in patients who underwent minimally invasive discectomy. MethodsPatients were divided into satisfied and dissatisfied subgroups based on Oswestry Disability Index (ODI), visual analogue scale (VAS) back pain score (VAS-back) and leg pain score (VAS-leg) at short-term and midterm follow-up according to the patient acceptable symptom state threshold. Demographic characteristics, radiographic parameters, and clinical outcomes between the satisfied and dissatisfied subgroups were compared using univariate and multivariate analysis. ResultsA total of 222 patients (92.1%) completed 2-year follow-up, and the postoperative ODI, VAS-back, and VAS-leg were significantly improved after surgery as compared to preoperatively. Multivariate analysis indicated older age (p=0.026), lateral recess stenosis (p=0.046), and lower baseline ODI (p=0.027) were related to poor short-term functional improvement. Higher baseline VAS-back (p=0.048) was associated with poor short-term relief of back pain, while absence of decreased sensation (p=0.019) and far-lateral disc herniation (p=0.004) were associated with poorer short-term relief of leg pain. Lumbar facet joint osteoarthritis was identified as a risk factor for poor functional improvement (p=0.003) and relief of back pain (p=0.031). Disc protrusion (p=0.036) predicted poorer relief of back pain at midterm follow-up. ConclusionIn this study, several factors were identified to be predictive of poor surgical outcomes following minimally invasive discectomy. (ClinicalTrials.gov number: NCT01997086).

COMPREHENSIVE ANALYSIS OF MICRO-RIBONUCLEIC ACID EXPRESSION IN LUMBAR FACET JOINT CAPSULES AND SYNOVIUM OF PATIENTS WITH OSTEOARTHRITIS

Purpose: MicroRNA is attracting attention as a therapeutic target for osteoarthritis. We focused on joint capsules and synovium in lumbar facet joint osteoarthritis. The objective of this study was a comprehensive analysis of microRNA in the facet joint capsule and synovium.

BAG3 protects chondrocytes against lumbar facet joint osteoarthritis by regulating autophagy and apoptosis.

Bcl2-associated athanogene3 (BAG3) protein, mainly induced by stressful stimuli, has been confirmed to participate in apoptosis and autophagy. In recent studies, BAG3 has gradually become a key molecule in tumors. However, the role of BAG3 in the progression of lumbar facet joint osteoarthritis (FJOA) and whether it can regulate chondrocyte apoptosis and autophagy are still unknown. In both human and FJOA rat models, we observed an upregulation of BAG3 and apoptosis and autophagy-related proteins compared with healthy tissues. Then, we established the chondrocytes injury model in vitro by using IL-1β to stimulate human SW1353 cells. Western blot analysis data showed significant expression of BAG3, apoptosis, and autophagy-related proteins in SW1353 cells. Finally, by knocking down and overexpressing BAG3, we discovered possible anti-apoptotic and autophagy-promoted effects of BAG3 in FJOA through various experimental methods. This study demonstrated that BAG3 actively participates in regulating chondrocyte apoptosis and autophagy in FJOA and may be a highly interesting targetfor pharmacological interventions.

Localization of Nerve Growth Factor Expression to Structurally Damaged Cartilaginous Tissues in Human Lumbar Facet Joint Osteoarthritis.

PurposeNerve Growth Factor (NGF) is a pivotal mediator of chronic pain and plays a role in bone remodelling. Through its high affinity receptor TrkA, NGF induces substance P (SP) as key downstream mediator of pain and local inflammation. Here we analysed NGF, TrkA and SP tissue distribution in facet joint osteoarthritis (FJOA), a major cause of chronic low back pain.MethodsFJOA specimens (n=19) were harvested from patients undergoing intervertebral fusion surgery. Radiologic grading of FJOA and spinal stenosis, followed by immunohistochemistry for NGF, TrkA and SP on consecutive tissue sections, was performed in ten specimens. Explant cultures (n=9) were used to assess secretion of NGF, IL-6, and SP by FJOA osteochondral tissues under basal and inflammatory conditions.ResultsNGF was predominantly expressed in damaged cartilaginous tissues (80%), occasionally in bone marrow (20%), but not in osteochondral vascular channels. NGF area fraction in cartilage was not associated with the extent of proteoglycan loss or radiologic FJOA severity. Consecutive sections showed that NGF and SP expression was localized at structurally damaged cartilage, in absence of TrkA expression. SP and TrkA were expressed in subchondral bone marrow in both presence and absence of NGF. Low level NGF, but not SP secretion, was detected in four out of eighteen FJOA explants under both basal or inflammatory conditions (n=2 each).ConclusionNGF is associated with SP expression and structural cartilage damage in osteoarthritic facet joints, but not with radiologic disease severity. NGF tissue distribution in FJOA differs from predominant subchondral bone expression reported for knee OA.

ANALYSIS OF RISK FACTORS AFFECTING LUMBAL FACET JOINT OSTEOARTHRITIS IN MRI SCAN

Background: Osteoarthritis is a long-term, chronic disease that is usually marked by cartilage degeneration in the joints, which in turn induces bone friction. One of the subtype of this disease is facet joint osteoarthritis or in short, FJOA. In Indonesia, FJOA has not been commonly documented. The most common method for FJOA inspection is X-Ray modality. The usage of other radiology imaging, such as CT-Scan or MRI, are also used to evaluate erosion, osteophyte creation, subchondral sclerosis, and joint constriction. Nevertheless, the most ideal FJOA inspection method is still an ongoing debate due to strengths and weaknesses of each methods. CT scans are more widely used than MRIs and are typically less expensive. MRIs, however, are thought to be superior in regards to the detail of the image. Objective: To understand the effect of age, sex, and spinal level towards FJOA on MRI scanning. Method: This research used cross-sectional approach. Sample taken in this research were all radiology results from patients that fulfills inclusion criteria and had gone through MRI inspection in Jatinegara Premier Hospital. Age, sex, disk degeneration degree, and spinal level are the main focus for this study since those are the most common risk factor for FJOA. Results: 46.8% of FJOA were found in male patients while the other 53.2% were found in females. L4-5 and Grade 1 FJOA had the highest incidence found, with the amount of 29% and 48.4% respectively. There was no correlation between sex and FJOA degree based on Asymp. Sig of 0.255. There was also no correlation between age and FJOA degree based on Asymp. Sig of 0.702. However, there was a correlation between spinal level and disk degeneration degree with FJOA degree due to Asymp. Sig &lt;0.05. Conclusion: There was no significant relationship between age and sex to lumbar facet joint osteoarthritis and there was a significant relationship between spinal level and disk degeneration degree with lumbar facet joint osteoarthritis.

Wnt16 protects chondrocytes from lumbar facet joint osteoarthritis through the Wnt/β-catenin pathway in low back pain patients

Purpose Low back pain (LBP) is a long-lasting and chronic symptom without any exact cause. This study attempts to propose a new staging system based on the original grading system combined with pathological results and clinical symptoms to better clarify the dynamic evolution of LBP related to cartilage degeneration during facet joint osteoarthritis (FJOA). To explore a potential target for diagnosis, treatment, and drug intervention of facet joint osteoarthritis related LBP via protecting chondrocytes. Materials and methods All the facet joints were divided into 4 groups according to our new degenerative staging system based on Weishaupt grade, CT and MRI. Collect the facet joint samples from patients whom suffered lumbar fusion surgery for lumbar disc herniation. Molecular biology experiments were used to explore the effect of Wnt16 on the degeneration of facet joints. Micro-CT examination and pain stimulation test checked the biological function of Wnt16 in rats. Results Wnt16 was significantly increased and more aggregated in the facet joint chondrocytes in the Phase III and Phase IV, which is consistent with the pathological findings of cartilage degeneration (OARSI). We found that Wnt16 participated in the regulation of FJOA via Wnt/β-catenin pathway in vitro, which was inhibited by specific inhibitor DKK1. The rats, rich expressed Wnt16, showed higher paw withdrawal thresholds and prolonged paw withdrawal latency to FJOA related LBP. Micro-CT examination for the lumbar spine of rats showed Wnt16 protected the chondrocytes from FJOA. Conclusions This study defined a new staging system for LBP related cartilage degeneration of facet joint based on the original grading system combined with pathological results and clinical symptoms. Wnt16 is expected to be a potential target for treatment of FJOA via protecting chondrocytes.

Knockdown of TRAF6 inhibits chondrocytes apoptosis and inflammation by suppressing the NF-κB pathway in lumbar facet joint osteoarthritis.

Tumor necrosis factor receptor-associated factor 6 (TRAF6), a regulator of NF-κB signaling, has been discovered recently to be probably related to osteoarthritis, while the function of TRAF6 in lumbar facet joint osteoarthritis(FJOA)still remains unknown. The aim of this study was to probe the specific function of TRAF6 in chondrocytes and its connection with the pathophysiology of FJOA. We found upregulation of TRAF6 in FJOA cartilage by western blot analysis. In vitro, we stimulated immortalized human chondrocytes by LPS to establish the cells apoptosis model. Western blot analysis demonstrated that levels of TRAF6 and cleaved caspase-3/8 in the chondrocyte injury model increased significantly. Knockdown of TRAF6 suppressed the expression of matrix metallopeptidase-13 (MMP-13) and interleukin-6 (IL-6) induced by LPS, and alleviated cell apoptosis. Meanwhile, western blot and immunofluorescent staining demonstrated that IκBα degradation and p65 nuclear transportation were also inhibited, revealing that knockdown of TRAF6 suppressed activation of the NF-κB pathway in LPS-induced chondrocytes apoptosis model. Collectively, our findings suggest that TRAF6 plays a crucial role in FJOA development by regulating NF-κB signaling pathway. Knockdown of TRAF6 may supply a potential therapeutic strategy for FJOA.

Characterization of the Subchondral Bone and Pain Behavior Changes in a Novel Bipedal Standing Mouse Model of Facet Joint Osteoarthritis.

Background The subchondral bone parallels with the progression of osteoarthritis (OA). However, the biomechanical properties and histopathological changes of subchondral bone changes in the lumbar facet joint (LFJ) after long-term axial loading on the spine have not been explored. In this study, we aimed to investigate the subchondral bone histopathological changes that occur in the LFJ and pain behaviors in a novel bipedal standing mouse model. Methods Sixteen 8-week-old male C57BL/6 mice were randomly assigned into bipedal standing and control groups. A finite element stimulate model based on the micro-CT data was generated to simulate the von Mises stress distribution on the LFJ during different positions. The spine pain behaviors tests were analysis. In addition, the change in the subchondral bone of the LFJ was assessed by histological and immunohistochemistry staining. Results The computerized simulation of the von Mises stress distribution in the superior articular process of LFJ at the spine level 5 in the lying position increased and reached a maximum value at the bipedal standing posture. The spine pain behavior test revealed that the threshold of pressure tolerance decreased significantly in bipedal groups relative to control groups, whereas the mechanical hyperalgesia of the hind paw increased significantly in bipedal groups relative to control groups. The axial load accelerates LFJ degeneration with increased histological scores in bipedal groups. The expression of type II collagen and aggrecan (ACAN) was significantly decreased in the bipedal groups compared with the control groups, whereas the expression of MMP13 was increased. Compared with the control groups, the osteoclast activity was activated with higher TRAP-positive staining and associated with increased CD-31-positive vessels and GCRP-positive nerve ending expression in the subchondral bone of LFJ. Conclusion Collectively, long-term axial loading induces the development of spine hyperalgesia in mice associate with increased osteoclast activity and aberrant angiogenesis and nerve invasion into the subchondral bone of LFJ that stimulates the natural pathological change in human LFJ OA. These results indicate that aberrant bone remodeling associate with aberrant nerve innervation in the subchondral bone has a potential as a therapeutic target in LFJ OA pain.

Development of a novel rat model of lumbar facet joint osteoarthritis induced by persistent compressive injury.

The aim of the present study was to develop a novel animal model of lumbar facet joint osteoarthritis induced by persistent compressive injury. An intraspinal compression spring was randomly implanted into either the L4/5 or the L5/6 spinal segments of 40 Sprague Dawley (SD) rats to induce compression. Sham-operations were used in the other segment of the same rats as the control levels. The animals were sacrificed at 7, 14, 28, 42 and 56 days after surgery, prior to the radiological confirmation of the spring location. Degeneration of the lumbar facet joints was evaluated by macroscopic observation in addition to histological and immunohistological analyses. The results of this present study revealed the absence of spring dislocation during the entire observation period. Macroscopic and Osteoarthritis Research Society International scores of the compression levels were found to be higher in the compression levels compared with those noted in the control levels (P<0.05). In addition, interleukin-1β and tumor necrosis factor-α expression in the compression levels were increased over time compared with those recorded in the control levels. In conclusion, persistent compressive injury may induce degeneration of the lumbar facet joint. This novel animal model could serve as a useful tool for further studies into the mechanisms of action and potential treatment of lumbar facet joint osteoarthritis.

Association between lumbar disc herniation and facet joint osteoarthritis

BackgroundThis study was performed to investigate the association between lumbar disc herniation (LDH) and facet joint osteoarthritis (FJOA) using magnetic resonance imaging (MRI).MethodsBetween March 2012 and September 2018, a total of 441 segments from 394 patients with LDH were included in the study. LDH was classified according to the Michigan State University (MSU) classification, in which the degree of LDH is divided into 3 levels (expressed as 1, 2, and 3) and the location of LDH is divided into 4 zones (described as A, AB, B, and C). Bilateral FJOA was graded from 0 to 3 using the criteria introduced by Weishaupt et al., and bilateral facet orientations were measured on axial MRI slices. A mixed-effects ordinal logistic regression model was utilized to determine the potential factors that may be associated with FJOA, including sex, age, body mass index (BMI), segment, facet orientation and tropism, and the degree and location of LDH.ResultsIn general, the prevalence of FJOA (grade ≥ 2) was 66.2% in LDH segments. For both the left and right sides, the degree of LDH was associated with the severity of FJOA (p < 0.01). Age and BMI were also associated with the severity of left and right FJOA (p = 0.002 and p < 0.001 for age, p < 0.001 and p = 0.003 for BMI, respectively), while segment, facet orientation, and facet tropism were not (p > 0.05 for all). Notably, MSU-B LDH was associated with greater odds of having more severe FJOA on the herniation side (left: p < 0.001, odds ratio (OR) = 2.714, 95% confidence interval (CI) = 1.583~4.650; right: p = 0.003, OR = 2.615, 95% CI = 1.405~4.870). However, other locations of LDH were not associated with the severity of FJOA (p > 0.05 for all).ConclusionsBoth the degree of LDH and MSU-B LDH are associated with the severity of FJOA. The association between LDH and FJOA highlights the complexity of the etiology of FJOA.

BMSCs-Derived Exosomes Ameliorate Pain Via Abrogation of Aberrant Nerve Invasion in Subchondral Bone in Lumbar Facet Joint Osteoarthritis.

Lumbar facet joint osteoarthritis (LFJ OA) is regarded as one of the common causes of low back pain (LBP). The pathogenesis and underlying mechanism of this disease are largely unknown, there is still no effective disease-modifying therapy. This study aims to investigate the efficacy of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) on the pathogenesis and behavioral signs of LBP in the LFJ OA mouse model. The pathogenetic change in cartilage and aberrant nerve invasion in the subchondral bone of LFJ in a mouse model after treatment with BMSC-exosomes was evaluated.BMSC-exosomes could relieve pain via abrogation of aberrant CGRP-positive nerve and abnormal H-type vessel formation in the subchondral bone of LFJ. Moreover, BMSC-exosomes attenuated cartilage degeneration and inhibited tartrate-resistant acid phosphatase expression and RANKL-RANK-TRAF6 signaling activation to facilitate subchondral bone remodeling. These results indicated that BMSC-exosomes could relive behavioral signs of LBP and pathological processes in LFJ OA. BMSC-exosomes have a prominent protective effect and might be a potential therapeutic option for the treatment of LFJ OA causing LBP. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:670-679, 2020.

Outcome of intra-articular lumbar facet joint corticosteroid injection according to the severity of facet joint arthritis.

Lumbar facet joint osteoarthritis (FJOA) caused by degenerative change(s) is considered to be the main cause of facet joint-origin low back pain (LBP). Intra-articular lumbar facet joint (IA LFJ) corticosteroid injection is widely used for controlling pain induced by FJOA. In the current study, the outcomes of IA LFJ corticosteroid injection were evaluated according to the severity of FJOA. A total of 50 patients who received IA LFJ corticosteroid injections for the treatment of LFJ pain were recruited. Patients were classified into three groups according to the severity of FJOA, which was indicated during a lumbar axial MRI. A total of 10 patients were assigned to group A (patients with mild FJOA), 27 to group B (patients with moderate FJOA) and 13 to group C (patients with severe FJOA). Pain intensity was evaluated using a numerical rating scale (NRS) prior to treatment and at 1, 2 and 3 months after treatment. A total of 26 (52%) patients experienced successful treatment outcomes (defined as >50% reduction in NRS score at 3 months). Patients in all groups demonstrated a significant decrease in NRS scores at 1, 2 and 3 months after IA LFJ corticosteroid injection compared with the pre-treatment score (P<0.001). However, the effect of IA LFJ corticosteroid injection was not significantly different among the three groups (P=0.889). The results demonstrated that facet joint-origin LBP was significantly reduced after IA LFJ corticosteroid injection, regardless of the severity of FJOA. The results of the current study indicated that IA LFJ corticosteroid injection is a beneficial clinical option for managing LBP caused by FJOA.

Unilateral Osteotomy of Lumbar Facet Joint Induces a Mouse Model of Lumbar Facet Joint Osteoarthritis

The lumbar facet joint (LFJ) osteoarthritis (OA) model that highly mimics the clinical conditions was established and evaluated. Here, we innovatively constructed and evaluated the aberrant mechanical loading-related LFJ OA model. LFJ is the only true synovial joint in a functional spinal unit in mammals. The LFJ osteoarthritis is considered to contribute 15% to 45% of low back pain. The establish of animal models highly mimicking the clinical conditions is a useful tool for the investigation of LFJ OA. However, the previously established animal models damaged the LFJ structure directly, which did not demonstrate the effect of aberrant mechanical loading on the development of LFJ osteoarthritis. In the present study, an animal model for LFJ degeneration was established by the unilateral osteotomy of LFJ (OLFJ) in L4/5 unit to induce the spine instability. Then, the change of contralateral LFJ was evaluated by morphological and molecular biological techniques. We showed that the OLFJ induced instability accelerated the cartilage degeneration of the contralateral LFJ. Importantly, the SRμCT elucidated that the three-dimensional structure of the subchondral bone changed in contralateral LFJ, indicated as the abnormity of bone volume/total volume ratio (BV/TV), trabecular pattern factor (Tb. Pf), and the trabecular thickness (Tb. Th). Immunostaining further demonstrated the uncoupled osteoclastic bone resorption, and bone formation in the subchondral bone of contralateral LFJ, indicated as increased activity of osteoclast, osteoblast, and Type H vessels. We develop a novel LFJ OA model demonstrating the effect of abnormal mechanical instability on the degeneration of LFJ. This LFJ degeneration model that highly mimics the clinical conditions is a valuable tool to investigate the LFJ osteoarthritis. N/A.

Relationship of joint hypermobility with low Back pain and lumbar spine osteoarthritis

BackgroundChronic low back pain (cLBP) affects millions of Americans and costs billions. Studies suggest a link between cLBP and joint hypermobility.MethodsWe conducted cross-sectional primary analyses of joint hypermobility and cLBP, lumbar spine osteoarthritis (OA), and lumbar facet joint OA (FOA) in 3 large studies—the Generalized Osteoarthritis Study, Genetics of Generalized Osteoarthritis Study, and Johnston County Osteoarthritis Project (total n = 5072). Associations of joint hypermobility and Beighton trunk flexion with cLBP and lumbar OA were estimated using separate adjusted logistic regression models. Adjusted pooled odds ratios (pORs) and 95% confidence intervals (CIs) were then summarized—using random effect univariate, multivariate crude, and adjusted models—and heterogeneity was determined (I2 statistic).ResultsIn univariate models, hypermobility was associated with symptomatic FOA (pOR = 0.64 [95% CI 0.44, 0.93]) but this result was not found in the multivariate models. In multivariate adjusted models, hypermobility was not significantly associated with cLBP and lumbar OA, but trunk flexion was inversely associated with cLBP (pOR = 0.40 [95% 0.26, 0.62]), spine OA (pOR = 0.66 [95% CI 0.50, 0.87]), symptomatic spine OA (pOR = 0.39 [95% CI 0.28, 0.53]), and symptomatic FOA (pOR = 0.53 [95% CI 0.37, 0.77]). Generally, between-study heterogeneity was moderate-high.ConclusionsHypermobility was not associated with cLBP or lumbar OA. The inverse association of trunk flexion with cLBP and lumbar OA may indicate a role for a flexible spine in avoiding or managing these conditions.

Salmon calcitonin exerts better preventive effects than celecoxib on lumbar facet joint degeneration and long-term tactile allodynia in rats.

To evaluate and compare the effects of salmon calcitonin (sCT) and celecoxib (CLX) on cartilage, subchondral bone and tactile allodynia in a rat model of lumbar facet joint (FJ) osteoarthritis (OA). Forty 3-month-old male Sprague-Dawley rats were randomly divided into four groups: 30 received surgical collagenase (type II) injections in the right L3-L6 facet joints followed by 8 weeks of treatment with normal saline, CLX or sCT, and the other 10 received sham surgery. Tactile allodynia, changes of cartilage and subchondral bone of the L4-L5 FJs, and serum biomarkers were analyzed for all rats. Both sCT and CLX ameliorated cartilage lesions, significantly increased aggrecan expression and decreased caspase-3 expression. sCT also decreased the expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4). According to the micro-computed tomography (micro-CT) analysis, sCT significantly improved microarchitecture parameters of subchondral bone and micro-CT score; and inhibited articular process hypertrophy. CLX showed better antihyperalgesic effects than sCT on days 3 and 7 postoperatively despite no statistical differences, whereas sCT possessed better analgesic effects than CLX on days 42 and 56. Besides, the sCT treatment reduced the elevated cartilage oligomeric matrix protein (COMP) concentration in rats injected with collagenase (type II). Both sCT and CLX exerted preventive effects on FJ OA caused by collagenase (type II), but sCT showed more protective effects, particularly on maintaining cartilage metabolism, restraining the deterioration of the subchondral bone microarchitecture and tactile allodynia, and reducing serum COMP concentrations.

Increased Substance P Immunoreactivity in Ipsilateral Knee Cartilage of Rats Exposed to Lumbar Spine Injury

The present study aimed to investigate whether experimentally induced lumbar facet-joint OA lead to degenerative changes and enhanced SP expression within the ipsilateral neurosegmentally linked tibiofemoral cartilage. Adult male Sprague-Dawley rats were assigned to left side L5-L6 facet mechanical compression injury (surgery) (n = 6), L5-L6 facet exposure with no compression (sham) (n = 5), or naïve (no surgery) (n = 4) groups. The morphology of the tibiofemoral articular cartilage was assessed using a modified Mankin scoring system. Immunohistochemistry was used to examine the density of chondrocytes stained positive for SP (cells/cm2) in the ipsilateral tibiofemoral cartilage at 28 days postintervention. Tibiofemoral cartilage in the surgery group showed consistent loss of superficial zone chondrocytes, mild roughening of the articular surface and occasional chondrocyte clusters as well as a greater density of SP mainly in the superficial cartilage zone compared with sham and naïve groups, although they also had a basic SP-expression. Our results support the hypothesis that neurogenic mechanisms may mediate the spread of SP to neurosegmentally linked heterologous joints affecting the distal cartilage homeostasis. These findings contribute additional insight into the potential role of neurogenic inflammation with implications in the pathophysiology of chronic inflammatory joint disease and OA.

Up-regulation of TRAF2 inhibits chondrocytes apoptosis in lumbar facet joint osteoarthritis

Tumor necrosis factor receptor-associated factor 2 (TRAF2) has been demonstrated that it plays a significant role in cell death receptor signal transduction. The purpose of this study was to investigate the expression of TRAF2 and its possible role in FJOA. We observed an up-regulation of TRAF2 in FJOA by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) compared to normal tissues. In vitro, we used TNF-α to stimulate Human SW1353 chondrosarcoma cells to establish the chondrocytes injury model. Western blot analysis revealed significant expression of TRAF2 and cleaved caspase-3/8 in SW1353 cells. Co-localization of TRAF2/cleaved caspase-3/8 was detected in the cells injury model by double-labeling immunofluorescent staining. We demonstrated a possible anti-apoptotic effect of TRAF2 in chondrocyte apoptosis in FJOA by knockdown of its expression with siRNA. Moreover, TRAF2 knockdown was demonstrated to enhance TNF-α-induced apoptosis by flow cytometry assay. In conclusion, our results show that the up-regulation of TRAF2 may play an important role in the inhibition of chondrocyte apoptosis of FJOA.