IL-6 Reduces Spheroid Sizes of Osteophytic Cells Derived from Osteoarthritis Knee Joint via Induction of Apoptosis.

Osteophytes in osteoarthritis (OA) joints contribute to restriction of joint movement, joint pain, and OA progression, but little is known about osteophyte regulators. Examination of gene expression related to cartilage extracellular matrix, endochondral ossification, and growth factor signaling in articular cartilage and osteophytes obtained from OA knee joints showed that several genes such as COL1A1, VCAN, BGLAP, BMP8B, RUNX2, and SOST were overexpressed in osteophytes compared with articular cartilage. Ratios of mesenchymal stem/progenitor cells, which were characterized by co-expression of CD105 and CD166, were significantly higher in osteophytic cells than articular cells. A three-dimensional culture method for cartilage and osteophyte cells was developed by modification of cultures of self-assembled spheroid cell organoids (spheroids). These spheroids cultured in the media for mesenchymal stem cells containing transforming growth factor-ß3 showed characteristic morphologies and gene expression profiles of articular cartilage and osteophytes, respectively. The effects of IL-1ß, tumor necrosis factor-α, and IL-6 on the spheroids of articular and osteophytic cells were studied. To the best of our knowledge, they provide the first evidence that IL-6 suppresses the spheroid size of osteophytic cells by inducing apoptosis and reducing extracellular matrix molecules. These data show that IL-6 is the suppressor of osteophyte growth and suggest that IL-6 expression and/or activity are implicated in the regulation of osteophyte formation in pathologic joints.

OA susceptibility in mice is partially mediated by the gut microbiome, is transferrable via microbiome transplantation and is associated with immunophenotype changes.

OBJECTIVES: The Murphy Roths Large (MRL)/MpJ 'superhealer' mouse strain is protected from post-traumatic osteoarthritis (OA), although no studies have evaluated the microbiome in the context of this protection. This study characterised microbiome differences between MRL and wild-type mice, evaluated microbiome transplantation and OA and investigated microbiome-associated immunophenotypes. METHODS: Cecal material from mixed sex C57BL6/J (B6) or female MRL/MpJ (MRL) was transplanted into B6 and MRL mice, then OA was induced by disruption of the medial meniscus surgery (DMM). In other experiments, transplantation was performed after DMM and transplantation was performed into germ-free mice. Transplanted mice were bred through F2. OARSI, synovitis and osteophyte scores were determined blindly 8 weeks after DMM. 16S microbiome sequencing was performed and metagenomic function was imputed. Immunophenotypes were determined using mass cytometry. RESULTS: MRL-into-B6 transplant prior to DMM showed reduced OA histopathology (OARSI score 70% lower transplant vs B6 control), synovitis (60% reduction) and osteophyte scores (30% reduction) 8 weeks after DMM. When performed 48 hours after DMM, MRL-into-B6 transplant improved OA outcomes but not when performed 1-2 weeks after DMM. Protection was seen in F1 (60% reduction) and F2 progeny (30% reduction). Several cecal microbiome clades were correlated with either better (eg, Lactobacillus, R=-0.32, p=0.02) or worse (eg, Rikenellaceae, R=0.43, p=0.001) OA outcomes. Baseline immunophenotypes associated with MRL-into-B6 transplants and MRL included reduced double-negative T cells and increased CD25+CD4+ T cells. CONCLUSION: The gut microbiome is responsible in part for OA protection in MRL mice and is transferrable by microbiome transplantation. Transplantation induces resting systemic immunophenotyping changes that correlate with OA protection.

2023 EULAR classification criteria for hand osteoarthritis.

OBJECTIVES: The objective of this study is to develop classification criteria for overall hand osteoarthritis (OA), interphalangeal OA and thumb base OA based on self-reported data and radiographic features. METHODS: The classification criteria sets were developed in three phases. In phase 1, we identified criteria that discriminated hand OA from controls. In phase 2, we used a consensus-based decision analysis approach to derive a clinician-based evaluation of the relative importance of the criteria. In phase 3, we refined the scoring system, determined the cut-offs for disease classification and compared the sensitivity and specificity of the European Alliance of Associations for Rheumatology (EULAR) criteria with the 1990 American College of Rheumatology (ACR) criteria. RESULTS: In persons with hand symptoms and no other disease (including psoriasis) or acute injury that can explain the hand symptoms (mandatory criteria), hand OA can be classified based on age, duration of morning stiffness, number of joints with osteophytes and joint space narrowing, and concordance between symptoms and radiographic findings. Using a sum of scores based on each diagnostic element, overall hand OA can be classified if a person achieves 9 or more points on a 0-15 scale. The cut-off for interphalangeal OA and thumb base OA is 8 points. While the EULAR criteria demonstrated better sensitivity than the ACR criteria in the phase 1 data set, the performance of the two criteria sets was similar in two external cohorts. CONCLUSIONS: International experts developed the EULAR criteria to classify overall hand OA, interphalangeal OA and thumb base OA in clinical studies using a rigorous methodology.

Mild exercise expedites joint clearance and slows joint degradation in a joint instability model of osteoarthritis in male rats.

OBJECTIVE: Exercise remains a hallmark treatment for post-traumatic osteoarthritis (PTOA) and may maintain joint homeostasis in part by clearing inflammatory cytokines, cells, and particles. It remains largely unknown whether exercise-induced joint clearance can provide therapeutic relief of PTOA. In this study, we hypothesized that exercise could slow the progression of preclinical PTOA in part by enhancing knee joint clearance. DESIGN: Surgical medial meniscal transection was used to induce PTOA in 3-month-old male Lewis rats. A sham surgery was used as a control. Mild treadmill walking was introduced 3 weeks post-surgery and maintained to 6 weeks post-surgery. Gait and isometric muscle torque were measured at the study endpoint. Near-infrared imaging tracked how exercise altered lymphatic and venous knee joint clearance during discrete time points of PTOA progression. RESULTS: Exercise mitigated joint degradation associated with PTOA by preserving glycosaminoglycan content and reducing osteophyte volume (effect size (95% Confidence Interval (CI)); 1.74 (0.71-2.26)). PTOA increased hind step widths (0.57 (0.18-0.95) cm), but exercise corrected this gait dysfunction (0.54 (0.16-0.93) cm), potentially indicating pain relief. Venous, but not lymphatic, clearance was quicker 1-, 3-, and 6-weeks post-surgery compared to baseline. The mild treadmill walking protocol expedited lymphatic clearance rate in moderate PTOA (3.39 (0.20-6.59) hrs), suggesting exercise may play a critical role in restoring joint homeostasis. CONCLUSIONS: We conclude that mild exercise has the potential to slow disease progression in part by expediting joint clearance in moderate PTOA.

Surgical restabilization reduces the progression of post-traumatic osteoarthritis initiated by ACL rupture in mice.

OBJECTIVE: People who sustain joint injuries such as anterior cruciate ligament (ACL) rupture often develop post-traumatic osteoarthritis (PTOA). In human patients, ACL injuries are often treated with ACL reconstruction. However, it is still unclear how effective joint restabilization is for reducing the progression of PTOA. The goal of this study was to determine how surgical restabilization of a mouse knee joint following non-invasive ACL injury affects PTOA progression. DESIGN: In this study, 187 mice were subjected to non-invasive ACL injury or no injury. After injury, mice underwent restabilization surgery, sham surgery, or no surgery. Mice were then euthanized on day 14 or day 49 after injury/surgery. Functional analyses were performed at multiple time points to assess voluntary movement, gait, and pain. Knees were analyzed ex vivo with micro-computed tomography, RT-PCR, and whole-joint histology to assess articular cartilage degeneration, synovitis, and osteophyte formation. RESULTS: Both ACL injury and surgery resulted in loss of epiphyseal trabecular bone (-27-32%) and reduced voluntary movement at early time points. Joint restabilization successfully lowered OA score (-78% relative to injured at day 14, p < 0.0001), and synovitis scores (-37% relative to injured at day 14, p = 0.042), and diminished the formation of chondrophytes/osteophytes (-97% relative to injured at day 14, p < 0.001, -78% at day 49, p < 0.001). CONCLUSIONS: This study confirmed that surgical knee restabilization was effective at reducing articular cartilage degeneration and diminishing chondrophyte/osteophyte formation after ACL injury in mice, suggesting that these processes are largely driven by joint instability in this mouse model. However, restabilization was not able to mitigate the early inflammatory response and the loss of epiphyseal trabecular bone, indicating that these processes are independent of joint instability.

Relationships between diagnostic imaging of first carpometacarpal osteoarthritis and pain, functional status, and disease progression: A systematic review.

OBJECTIVE: To systematically review the association of pain, function, and progression in first carpometacarpal (CMC) osteoarthritis (OA) with imaging biomarkers and radiography-based staging. DESIGN: Database searches in PubMed, Embase, and the Cochrane Library, along with citation searching were conducted in accordance with published guidance. Data on the association of imaging with pain, functional status, and disease progression were extracted and synthesized, along with key information on study methodology such as sample sizes, use of control subjects, study design, number of image raters, and blinding. Methodological quality was assessed using National Heart, Lung, and Blood Institute tools. RESULTS: After duplicate removal, a total of 1969 records were screened. Forty-six articles are included in this review, covering a total of 28,202 study participants, 7263 with first CMC OA. Osteophytes were found to be one of the strongest biomarkers for pain across imaging modalities. Radiographic findings alone showed conflicting relationships with pain. However, Kellgren-Lawrence staging showed consistent associations with pain in various studies. Radiographic, sonographic, and MRI findings and staging showed little association to tools evaluating functional status across imaging modalities. The same imaging methods showed limited ability to predict progression of first CMC OA. A major limitation was the heterogeneity in the study base, limiting synthesis of results. CONCLUSION: Imaging findings and radiography-based staging systems generally showed strong associations with pain, but not with functional status or disease progression. More research and improved imaging techniques are needed to help physicians better manage patients with first CMC OA.

Comparing CT-Like Images Based on Ultra-Short Echo Time and Gradient Echo T1-Weighted MRI Sequences for the Assessment of Vertebral Disorders Using Histology and True CT as the Reference Standard.

BACKGROUND: Several magnetic resonance (MR) techniques have been suggested for radiation-free imaging of osseous structures. PURPOSE: To compare the diagnostic value of ultra-short echo time and gradient echo T1-weighted MRI for the assessment of vertebral pathologies using histology and computed tomography (CT) as the reference standard. STUDY TYPE: Prospective. SUBJECTS: Fifty-nine lumbar vertebral bodies harvested from 20 human cadavers (donor age 73 ± 13 years; 9 male). FIELD STRENGTH/SEQUENCE: Ultra-short echo time sequence optimized for both bone (UTEb) and cartilage (UTEc) imaging and 3D T1-weighted gradient-echo sequence (T1GRE) at 3 T; susceptibility-weighted imaging (SWI) gradient echo sequence at 1.5 T. CT was performed on a dual-layer dual-energy CT scanner using a routine clinical protocol. ASSESSMENT: Histopathology and conventional CT were acquired as standard of reference. Semi-quantitative and quantitative morphological features of degenerative changes of the spines were evaluated by four radiologists independently on CT and MR images independently and blinded to all other information. Features assessed were osteophytes, endplate sclerosis, visualization of cartilaginous endplate, facet joint degeneration, presence of Schmorl's nodes, and vertebral dimensions. Vertebral disorders were assessed by a pathologist on histology. STATISTICAL TESTS: Agreement between T1GRE, SWI, UTEc, and UTEb sequences and CT imaging and histology as standard of reference were assessed using Fleiss' κ and intra-class correlation coefficients, respectively. RESULTS: For the morphological assessment of osteophytes and endplate sclerosis, the overall agreement between SWI, T1GRE, UTEb, and UTEc with the reference standard (histology combined with CT) was moderate to almost perfect for all readers (osteophytes: SWI, κ range: 0.68-0.76; T1GRE: 0.92-1.00; UTEb: 0.92-1.00; UTEc: 0.77-0.85; sclerosis: SWI, κ range: 0.60-0.70; T1GRE: 0.77-0.82; UTEb: 0.81-0.92; UTEc: 0.61-0.71). For the visualization of the cartilaginous endplate, UTEc showed the overall best agreement with the reference standard (histology) for all readers (κ range: 0.85-0.93). DATA CONCLUSIONS: Morphological assessment of vertebral pathologies was feasible and accurate using the MR-based bone imaging sequences compared to CT and histopathology. T1GRE showed the overall best performance for osseous changes and UTEc for the visualization of the cartilaginous endplate. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

ILK inhibition reduces osteophyte formation through suppression of osteogenesis in BMSCs via Akt/GSK-3ß/ß-catenin pathway.

BACKGROUND: Osteophyte development is a common characteristic of inflammatory skeletal diseases. Elevated osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) participates in pathological osteogenesis. Integrin-linked kinase (ILK) positively regulates the osteoblastic differentiation of osteoprogenitors, but whether the ILK blockage prevents osteophytes and its potential mechanism is still unknown. Furthermore, the low-dose tumor necrosis factor-α (TNF-α) promotes osteogenic differentiation, but a lack of study reports on the relationship between this cytokine and ILK. OSU-T315 is a small ILK inhibitor, which was used to determine the effect of ILK inhibition on osteogenesis and osteophyte formation. METHODS AND RESULTS: The osteogenesis of BMSCs was evaluated using Alizarin red S staining, alkaline phosphatase, collagen type I alpha 2 chain, and bone gamma-carboxyglutamate protein. The expression and phosphorylation of protein were assessed through western blot. Immunofluorescence was employed to display the distribution of ß-catenin. microCT, hematoxylin-eosin, and safranin O/fast green staining were utilized to observe the osteophyte formation in collagen antibody-induced arthritis mice. We found that ILK blockage significantly declined calcium deposition and osteoblastic markers in a dose- and time-dependent manner. Furthermore, it lowered osteogenesis in the TNF-α-induced inflammatory microenvironment by diminishing the effect of ILK and inactivating the Akt/ GSK-3ß/ ß-catenin pathway. Nuclear ß-catenin was descended by OSU-T315 as well. Finally, the ILK suppression restrained osteophyte formation but not inflammation in vivo. CONCLUSIONS: ILK inhibition lowered osteogenesis in TNF-α-related inflammatory conditions by deactivating the Akt/ GSK-3ß/ ß-catenin pathway. This may be a potential strategy to alleviate osteophyte development in addition to anti-inflammatory treatment.

Cervical anterior spinal artery infarction associated with anomalous vertebral artery: a case report.

We report a unique case of cervical anterior spinal artery (ASA) infarction in a 49-year-old male with hypercholesterolemia and sleep apnea. The patient experienced sudden cervical pain, quadriparesis, areflexia, and urinary incontinence after swallowing a large food bolus. Imaging revealed an infarction at the C3-C5 levels and an anomalous right vertebral artery (VA) originating from the thoracic aorta, tightly enclosed between the aorta and a vertebral column with an anterior osteophyte. This aberrant VA was the primary vascular supply to the ASA, with no contribution from the left VA or supreme intercostal arteries. We propose that transient injury to the right VA, induced by compression between the aortic arch, the food bolus, and the osteophyte, led to temporary hypoperfusion of the ASA, causing a watershed ischemic injury in the mid cervical cord's anterior gray matter. The article also provides an in-depth discussion of the developmental and clinical characteristics associated with this rare vascular anomaly.

The Relationship between Bony Changes of the Mandibular Condyle and Eichner Index.

INTRODUCTION: The aim of this study was to evaluate whether degenerative bone changes in the mandibular condyle on cone beam computed tomography images are associated with the Eichner index. METHODOLOGY: 336 cone beam computed tomography images condyle images of 168 patients were analyzed for degenerative bone changes. These changes were named as condyle flattening, osteophytes, erosions, subchondral sclerosis, generalized sclerosis and subchondral cysts. The edentulous status of the patients was classified as group A-B-C and subtypes according to the Eichner index. Categorical variables were evaluated with chi-square test and p < 0.05 was considered statistically significant. RESULTS: According to the results of the study, the most common degenerative condyle change was flattening of the condyle. Among the Eichner index groups, the most common group was A and the least common group was C. Condyle changes on the right and left sides were most commonly observed in group A patients. The statistically significant majority of patients with right-sided condyle flattening and erosion were in group C. No significant difference was found between all other condyle changes and Eichner index groups. There was no significant relationship between Eichner index and gender. CONCLUSION: Degenerative bone changes (flattening and erosion of the condyle) in the condyle region were more common in group C patients with more tooth loss. There is a significant relationship between condyle changes and posterior toothlessness.

The relationship between MRI-detected hip abnormalities and hip pain in hip osteoarthritis: a systematic review.

Magnetic resonance imaging (MRI) is increasingly used in the classification and evaluation of osteoarthritis (OA). Many studies have focused on knee OA, investigating the association between MRI-detected knee structural abnormalities and knee pain. Hip OA differs from knee OA in many aspects, but little is known about the role of hip structural abnormalities in hip pain. This study aimed to systematically evaluate the association of hip abnormalities on MRI, such as cartilage defects, bone marrow lesions (BMLs), osteophytes, paralabral cysts, effusion-synovitis, and subchondral cysts, with hip pain. We searched electronic databases from inception to February 2024, to identify publications that reported data on the association between MRI features in the hip joint and hip pain. The quality of the included studies was scored using the Newcastle-Ottawa Scale (NOS). The levels of evidence were evaluated according to the Cochrane Back Review Group Method Guidelines and classified into five levels: strong, moderate, limited, conflicting, and no evidence. A total of nine studies were included, comprising five cohort studies, three cross-sectional studies, and one case-control study. Moderate level of evidence suggested a positive association of the presence and change of BMLs with the severity and progress of hip pain, and evidence for the associations between other MRI features and hip pain were limited or even conflicting. Only a few studies with small to modest sample sizes evaluated the association between hip structural changes on MRI and hip pain. BMLs may contribute to the severity and progression of hip pain. Further studies are warranted to uncover the role of hip MRI abnormalities in hip pain. The protocol for the systematic review was registered with PROSPERO ( https://www.crd.york.ac.uk/PROSPERO/ , CRD42023401233).

Intercondylar notch width and osteophyte width impact meniscal healing and clinical outcomes following transtibial pullout repair of medial meniscus posterior root tears.

PURPOSE: This retrospective study aimed to investigate the relationship between intercondylar notch width (ICNW), osteophyte width (OW), and the healing of medial meniscus posterior root tears (MMPRTs) following arthroscopic pullout repair. METHODS: The study included 155 patients diagnosed with MMPRTs who underwent transtibial pullout repair. Meniscal healing status was evaluated on second-look arthroscopy using a previously reported meniscus healing score. Patients were divided into two groups based on this score: the high healing score (group HH, healing score ≥ 8 points) and suboptimal healing score (group SO, healing score ≤ 6 points) groups. Computed tomography scans were performed on patients 1 week postsurgery. ICNW and OW widths were measured and relatively evaluated based on their ratio to the intercondylar distance (ICD), represented as the ICNW/ICD ratio (%) and OW/ICD ratio (%), respectively. Patient-reported outcomes were assessed preoperatively and on second-look arthroscopy using the Knee injury and Osteoarthritis Outcome Score (KOOS) and visual analogue scale (VAS). RESULTS: There were no significant demographic differences between the SO and HH group (n = 35 and 120 patients, respectively). Regarding radiographic measurements, significant differences were observed in the ICNW/ICD ratio (group SO, 24.2%; group HH, 25.2%; p = 0.024), OW (group SO, 2.6 mm; group HH, 2.0 mm; p < 0.001), and OW/ICD ratio (group SO, 3.5%; group HH, 2.7%; p < 0.001). Both groups had similar preoperative clinical scores, but postoperative clinical scores, including KOOS-activities of daily living (group SO, 83.4; group HH, 88.7; p = 0.035) and VAS (group SO, 19.1; group HH, 11.3; p = 0.005), were significantly better in group HH. CONCLUSION: The study suggests that ICNW and OW may play a crucial role in MMPRT healing following arthroscopic pullout repair, as evidenced by the worse clinical outcomes associated with a narrower ICNW and wider OW. These findings highlight the potential significance of ICNW and OW assessments when evaluating meniscal repair indications. LEVEL OF EVIDENCE: Level III.

Characterizing Osteophyte Formation in Knee Osteoarthritis: Application of Machine Learning Quantification of a Computerized Tomography Cohort: Implications for Treatment.

BACKGROUND: Osteophytes are commonly used to diagnose and guide knee osteoarthritis (OA) treatment, but their causes are unclear. Although they are not typically the focus of knee arthroplasty surgeons, they can predict case difficulty and length. Furthermore, their extent and location may yield much information about the knee joint status. The aims of this computed tomography-based study in patients awaiting total or partial knee arthroplasty were to: (1) measure osteophyte volume in anatomical subregions and relative change as total volume increases; (2) determine whether medial and/or lateral OA affects osteophyte distribution; and (3) explore relationships between osteophytes and OA severity. METHODS: Data were obtained from 4,928 computed tomography scans. Machine-learning-based imaging analyses enabled osteophyte segmentation and quantification, divided into anatomical regions. Mean three-dimensional joint space narrowing was assessed in medial and lateral compartments. A Bayesian model assessed the uniformity of osteophyte distribution. We correlated femoral osteophyte volumes with B-scores, a validated OA status measure. RESULTS: Total tibial (25%) and femoral osteophyte volumes (75%) within each knee correlated strongly (R2 = 0.85). Medial osteophytes (65.3%) were larger than lateral osteophytes (34.6%), with similar proportions in both the femur and tibia. Osteophyte growth was found in all compartments, and as total osteophyte volume increased, the relative distribution of osteophytes between compartments did not markedly change. No evidence of variation was found in the regional distribution of osteophyte volume between knees with medial, lateral, both, or no three-dimensional joint space narrowing in the femur or tibia. There was a direct relationship between osteophyte volume and OA severity. CONCLUSIONS: Osteophyte volume increased in both medial and lateral compartments proportionally with total osteophyte volume, regardless of OA location. The peripheral position of femoral osteophytes does not appear to contribute to load-bearing. This suggests that osteophytic growth represents a 'whole-knee'/global response. This work may have broad applications for knee OA, both surgically and nonoperatively.

Do voxel size and filter application on CBCT images improve the diagnosis of condylar morphological alterations? An ex vivo study.

BACKGROUND: There is no established protocol for the low doses of cone-beam computed tomography (CBCT) acquisition and filter application on the diagnosis of condylar morphological alterations. OBJECTIVES: The objective of the study was to evaluate the influence of voxel size and filter application on the diagnosis of condylar morphological alterations in CBCT using an ex vivo model. METHODS: CBCT scans of 36 temporomandibular joints were acquired using OP300 Maxio with voxel sizes of 0.085, 0.125 and 0.280 mm. Three radiologists evaluated the condyles in the CBCT volumes under three filter modes: no filter, '1x' sharpen filter and '2x' sharpen filter. The area under the ROC curve, sensitivity and specificity were calculated by comparing the evaluators' responses with the reference standard and compared among experimental groups using analysis of variance (ANOVA) (α = 5%). RESULTS: The area under the ROC curve, sensitivity and specificity were not affected by voxel size and filter application (p > .05). For osteophyte and flattening, there were more true-positive responses in smaller voxel size. For erosion, the increase of true- and false-positive responses occurred with a larger voxel size. Overall, there was a tendency to decrease true positives for osteophyte and erosion and increase false positives for flattening with the '2x' sharpen filter. CONCLUSIONS: The diagnosis of condylar morphological alterations assessed in this ex vivo analysis is not influenced by the voxel size and the application of the filters. However, attention is needed with the occurrence of false-positive diagnosis with a larger voxel size for erosion and '2x' sharpen filter for flattening.

Osteophyte Cartilage as a Potential Source for Minced Cartilage Implantation: A Novel Approach for Articular Cartilage Repair in Osteoarthritis.

Osteoarthritis (OA) is a common joint disorder characterized by cartilage degeneration, often leading to pain and functional impairment. Minced cartilage implantation (MCI) has emerged as a promising one-step alternative for large cartilage defects. However, the source of chondrocytes for MCI remains a challenge, particularly in advanced OA, as normal cartilage is scarce. We performed in vitro studies to evaluate the feasibility of MCI using osteophyte cartilage, which is present in patients with advanced OA. Osteophyte and articular cartilage samples were obtained from 22 patients who underwent total knee arthroplasty. Chondrocyte migration and proliferation were assessed using cartilage fragment/atelocollagen composites to compare the characteristics and regenerative potential of osteophytes and articular cartilage. Histological analysis revealed differences in cartilage composition between osteophytes and articular cartilage, with higher expression of type X collagen and increased chondrocyte proliferation in the osteophyte cartilage. Gene expression analysis identified distinct gene expression profiles between osteophytes and articular cartilage; the expression levels of COL2A1, ACAN, and SOX9 were not significantly different. Chondrocytes derived from osteophyte cartilage exhibit enhanced proliferation, and glycosaminoglycan production is increased in both osteophytes and articular cartilage. Osteophyte cartilage may serve as a viable alternative source of MCI for treating large cartilage defects in OA.

Disease-Modifying Effects of Lenvatinib, a Multiple Receptor Tyrosine Kinase Inhibitor, on Posttraumatic Osteoarthritis of the Knee.

Angiogenesis and vascular endothelial growth factor (VEGF) are involved in osteoarthritis (OA). We previously reported the inhibitory effect of bevacizumab in a rabbit model of OA. In the current study, we investigated the effects of lenvatinib, an angiogenesis inhibitor targeting the VEGF and fibroblast growth factor receptors, on synovitis, osteophyte formation, and cartilage degeneration in a rabbit OA model. Posttraumatic OA was induced by anterior cruciate ligament transection (ACLT) on one knee of each rabbit. Rabbits were placed into four groups according to the following lenvatinib doses: untreated control (n = 12), L0.3: 0.3 mg/kg/day (n = 15), L1.0: 1.0 mg/kg/day (n = 14), and L3.0: 3.0 mg/kg/day (n = 13) groups. We evaluated limb pain using the weight distribution ratio measured with an incapacitance tester, macroscopic osteophyte formation, and femoral condyle synovium and cartilage histology. For cartilage evaluation, the following distal sites of the femur were evaluated separately: femoral-tibial (FT), femoral-patellar (FP), and femoral corner (between FP and FT). The weight distribution ratio at 12 weeks after surgery was higher in the L0.3 and L1.0 groups than in the control group. Osteophyte formation and synovitis scores were significantly lower in the L0.3, L1.0, and L3.0 groups than in the control group. The Osteoarthritis Research Society International scores of the FT, corner, and FP sites in the L0.3 group were lower than in the control group. The cartilage thickness ratio at the FT and corner sites was significantly lower in the L0.3 group than in the control group. Krenn's grading system of cartilage synovitis showed that all lenvatinib-administered groups had significantly lower scores than the control group. MMP3 expression level in cartilage tissue was significantly lower in the L3.0 group compared with the other three groups. ADAMTS5 expression was lower in the L3.0 group compared with the control and L0.3 groups. Oral administration of lenvatinib inhibited synovitis, osteophyte formation, and cartilage degeneration and reduced pain in a rabbit ACLT model. Lenvatinib is an oral VEGF inhibitor that is easier to administer than other VEGF inhibitors and may have potential as a treatment of posttraumatic OA.

Hallux Dorsal Curvature of the Distal Phalanx and Its Possible Implications for the Dorsal Osteophyte.

Background and Objective: The dorsal osteophyte on the distal phalanx of the first toe (hallux) is a reactive bony protrusion that may be associated with pathologies such as onychocryptosis or pincer nail. This study aims to describe and analyze the correlation between three novel measurements-dorsal osteophyte height (HDO), distal phalangeal hyperextension (DPHA), and distal phalangeal curvature (DCDP)-and to evaluate the impact of minimally invasive surgery on the dorsal osteophyte using fluoroscopic data. Materials and Methods: A total of 125 fluoroscopic images were analyzed. Baseline measurements for the variables were compared between groups. The key variables included distal phalanx curvature, distal phalanx hyperextension, and dorsal osteophyte height. Results: The analysis revealed statistically significant differences in the main group effect for distal phalanx curvature (F [2, 122] = 7.54, p < 0.001), distal phalanx hyperextension (F [2, 122] = 28.90, p < 0.001), and dorsal osteophyte height (F [2, 122] = 13.64, p < 0.001). Significant correlations were found between distal phalanx curvature and distal phalanx hyperextension, as well as between distal phalanx hyperextension and dorsal osteophyte height. However, no significant correlation was observed between distal phalanx curvature and dorsal osteophyte height. Conclusions: The findings suggest that minimally invasive dorsal osteophyte surgery effectively restores the distal phalanx to normal conditions, as indicated by the variables studied.

Superior humeral head osteophytes are associated with rotator cuff insufficiency in glenohumeral osteoarthritis: a retrospective analysis.

PURPOSE: The primary goal of this study was to investigate whether superior humeral head osteophyte (SHO) size is associated with rotator cuff insufficiency, including rotator cuff tear (RCT), supraspinatus tendon thickness, and fatty infiltration of the rotator cuff muscles. METHODS: Patients ≥ 18 years who were diagnosed with glenohumeral osteoarthritis were retrospectively reviewed. SHO size was determined by radiograph. MRI measured SHO and RCT presence, type, and size; supraspinatus tendon thickness; and fatty infiltration of rotator cuff musculature. RESULTS: A total of 461 patients were included. Mean SHO size was 1.93 mm on radiographs and 2.13 mm on MRI. Risk ratio for a RCT was 1.14. For each 1-mm increase in SHO size on radiograph, supraspinatus tendon thickness decreased by 0.20 mm. SHO presence was associated with moderate-to-severe fatty infiltration of the supraspinatus with a risk ratio of 3.16. CONCLUSION: SHOs were not associated with RCT but were associated with higher risk of supraspinatus FI and decreased tendon thickness, which could indicate rotator cuff insufficiency. LEVEL OF EVIDENCE: IV.

[Dysphagia as the main symptom in anterior cervical spine osteophytes (Forestier disease and cervical spondylosis deformans). Case reports and literature review]. / Disfagiya kak osnovnoi simptom pri perednikh osteofitakh sheinogo otdela pozvonochnika (bolezn' Forest'e i tservikal'nyi deformiruyushchii spondilez): obzor literatury i analiz klinicheskikh sluchaev.

Anterior cervical osteophytes are a fairly common X-ray finding in people over 50 years old. Incidence of dysphagia in patients with anterior osteophytes varies from 1% in those aged 40-60 years to 10.6% in patients over 60 years old. The most common causes of anterior cervical hyperosteophytosis causing dysphagia are cervical spondylosis deformans and Forestier disease. We present 2 clinical cases of spondylogenic dysphagia in cervical spondylosis deformans and Forestier disease. The review is devoted to the causes and diagnostic methods for dysphagia caused by anterior cervical osteophytes, as well as surgical options for this pathology. CONCLUSION: Microsurgical resection of anterior osteophytes is an effective method for dysphagia after ineffective therapy for 3 months. Microsurgical osteophytectomy provides stable regression of dysphagia with low recurrence rate.

Cartilage-specific Sirt6 deficiency represses IGF-1 and enhances osteoarthritis severity in mice.

OBJECTIVES: Prior studies noted that chondrocyte SIRT6 activity is repressed in older chondrocytes rendering cells susceptible to catabolic signalling events implicated in osteoarthritis (OA). This study aimed to define the effect of Sirt6 deficiency on the development of post-traumatic and age-associated OA in mice. METHODS: Male cartilage-specific Sirt6-deficient mice and Sirt6 intact controls underwent destabilisation of the medial meniscus (DMM) or sham surgery at 16 weeks of age and OA severity was analysed at 6 and 10 weeks postsurgery. Age-associated OA was assessed in mice aged 12 and 18 months of age. OA severity was analysed by micro-CT, histomorphometry and scoring of articular cartilage structure, toluidine blue staining and osteophyte formation. SIRT6-regulated pathways were analysed in human chondrocytes by RNA-sequencing, qRT-PCR and immunoblotting. RESULTS: Sirt6-deficient mice displayed enhanced DMM-induced OA severity and accelerated age-associated OA when compared with controls, characterised by increased cartilage damage, osteophyte formation and subchondral bone sclerosis. In chondrocytes, RNA-sequencing revealed that SIRT6 depletion significantly repressed cartilage extracellular matrix (eg, COL2A1) and anabolic growth factor (eg, insulin-like growth factor-1 (IGF-1)) gene expression. Gain-of-function and loss-of-function studies in chondrocytes demonstrated that SIRT6 depletion attenuated, whereas adenoviral overexpression or MDL-800-induced SIRT6 activation promoted IGF-1 signalling by increasing Aktser473 phosphorylation. CONCLUSIONS: SIRT6 deficiency increases post-traumatic and age-associated OA severity in vivo. SIRT6 profoundly regulated the pro-anabolic and pro-survival IGF-1/Akt signalling pathway and suggests that preserving the SIRT6/IGF-1/Akt axis may be necessary to protect cartilage from injury-associated or age-associated OA. Targeted therapies aimed at increasing SIRT6 function could represent a novel strategy to slow or stop OA.