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Arthritis Care & Research Jul 2023Meniscal tear in persons aged ≥45 years is typically managed with physical therapy (PT), and arthroscopic partial meniscectomy (APM) is offered to those who do not...
OBJECTIVE
Meniscal tear in persons aged ≥45 years is typically managed with physical therapy (PT), and arthroscopic partial meniscectomy (APM) is offered to those who do not respond. Prior studies suggest APM may be associated with greater progression of radiographic changes.
METHODS
We assessed changes between baseline and 60 months in the Kellgren-Lawrence (KL) grade and OARSI radiographic score (including subscores for joint space narrowing and osteophytes) in subjects aged 45-85 years enrolled into a seven-center randomized trial comparing outcomes of APM with PT for meniscal tear, osteoarthritis changes, and knee pain. The primary analysis classified subjects according to treatment received. To balance APM and PT groups, we developed a propensity score and used inverse probability weighting (IPW). We imputed a 60-month change in the OARSI score for subjects who underwent total knee replacement (TKR). In a sensitivity analysis, we classified subjects by randomization group.
RESULTS
We analyzed data from 142 subjects (100 APM, 42 PT). The mean ± SD weighted baseline OARSI radiographic score was 3.8 ± 3.5 in the APM group and 4.0 ± 4.9 in the PT group. OARSI scores increased by a mean of 4.1 (95% confidence interval [95% CI] 3.5-4.7) in the APM group and 2.4 (95% CI 1.7-3.2) in the PT group (P < 0.001) due to changes in the osteophyte component. We did not observe statistically significant differences in the KL grade. Sensitivity analyses yielded similar findings to the primary analysis.
CONCLUSION
Subjects treated with APM had greater progression in the OARSI score because of osteophyte progression but not in the KL grade. The clinical implications of these findings require investigation.
PubMed: 37474452
DOI: 10.1002/acr.25197 -
Annals of the Rheumatic Diseases Feb 2024The Murphy Roths Large (MRL)/MpJ 'superhealer' mouse strain is protected from post-traumatic osteoarthritis (OA), although no studies have evaluated the microbiome in...
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, R=-0.32, p=0.02) or worse (eg, , 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.
Topics: Mice; Female; Animals; Gastrointestinal Microbiome; Osteophyte; Immunophenotyping; Microbiota; Synovitis; Disease Models, Animal; Mice, Inbred C57BL; Cartilage, Articular
PubMed: 37979958
DOI: 10.1136/ard-2023-224907 -
Skeletal Radiology Nov 2023A joint contains many different tissues that can exhibit pathological changes, providing many potential targets for treatment. Researchers are increasingly suggesting... (Review)
Review
A joint contains many different tissues that can exhibit pathological changes, providing many potential targets for treatment. Researchers are increasingly suggesting that osteoarthritis (OA) comprises several phenotypes or subpopulations. Consequently, a treatment for OA that targets only one pathophysiologic abnormality is unlikely to be similarly efficacious in preventing or delaying the progression of all the different phenotypes of structural OA. Five structural phenotypes have been proposed, namely the inflammatory, meniscus-cartilage, subchondral bone, and atrophic and hypertrophic phenotypes. The inflammatory phenotype is characterized by marked synovitis and/or joint effusion, while the meniscus-cartilage phenotype exhibits severe meniscal and cartilage damage. Large bone marrow lesions characterize the subchondral bone phenotype. The hypertrophic and atrophic OA phenotype are defined based on the presence large osteophytes or absence of any osteophytes, respectively, in the presence of concomitant cartilage damage. Limitations of the concept of structural phenotyping are that they are not mutually exclusive and that more than one phenotype may be present. It must be acknowledged that a wide range of views exist on how best to operationalize the concept of structural OA phenotypes and that the concept of structural phenotypic characterization is still in its infancy. Structural phenotypic stratification, however, may result in more targeted trial populations with successful outcomes and practitioners need to be aware of the heterogeneity of the disease to personalize their treatment recommendations for an individual patient. Radiologists should be able to define a joint at risk for progression based on the predominant phenotype present at different disease stages.
Topics: Humans; Osteoarthritis, Knee; Knee Joint; Osteophyte; Magnetic Resonance Imaging; Cartilage, Articular; Hypertrophy; Cartilage Diseases; Bone Diseases; Phenotype
PubMed: 36161341
DOI: 10.1007/s00256-022-04191-6 -
International Journal of Molecular... Jun 2024Angiogenesis and vascular endothelial growth factor (VEGF) are involved in osteoarthritis (OA). We previously reported the inhibitory effect of bevacizumab in a rabbit...
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 ( = 12), L0.3: 0.3 mg/kg/day ( = 15), L1.0: 1.0 mg/kg/day ( = 14), and L3.0: 3.0 mg/kg/day ( = 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.
Topics: Animals; Rabbits; Quinolines; Phenylurea Compounds; Osteoarthritis, Knee; Protein Kinase Inhibitors; Disease Models, Animal; Male; Synovitis; Cartilage, Articular; Osteophyte; Tyrosine Kinase Inhibitors
PubMed: 38928219
DOI: 10.3390/ijms25126514 -
Osteoarthritis and Cartilage Open Dec 2023Osteophyte formation is attracting attention as an early-stage pathology of knee osteoarthritis (OA). Although osteophyte formation is understood as a defense response...
BACKGROUND
Osteophyte formation is attracting attention as an early-stage pathology of knee osteoarthritis (OA). Although osteophyte formation is understood as a defense response to joint instability, its role and impact on OA remain largely unknown. Many studies have been conducted using the surgical destabilization of the medial meniscus (DMM) mouse model, but there are few standard evaluation methods, especially in the histological evaluation of early-stage osteophytes. The purpose of this study was to establish a reproducible and uniform method for histological evaluation of characteristics of early osteophyte formation in the DMM mouse model.
METHODS
Male mice were operated with DMM at 12 weeks old and histologically evaluated at 4 days and 1, 2 and 4 weeks after DMM. Osteophyte Width, Osteophyte Area, and Original and Modified Maturity Scores were used to evaluate osteophytes for all sections.
RESULTS
Osteophyte Width, Osteophyte Area and Maturity Scores were all greater anteriorly than posteriorly in the knee joint. The Modified Maturity Score was more strongly correlated with position than the Original Maturity Score, and could be used to evaluate early-stage osteophyte formation.
CONCLUSION
The Modified Maturity Score as well as Osteophyte Width and Area at the section of the anterior cruciate ligament (ACL) attachment site can provide a reproducible evaluation method to histologically assess the early-stage osteophyte formation in the DMM mouse model.
PubMed: 37767107
DOI: 10.1016/j.ocarto.2023.100409 -
Advances in Clinical and Experimental... Jan 2024Degenerative disease of the spine (DDS) is one of the most common pathological conditions in humans. The clinical presentation of DDS is highly variable, ranging from... (Review)
Review
Degenerative disease of the spine (DDS) is one of the most common pathological conditions in humans. The clinical presentation of DDS is highly variable, ranging from mild pain to severe neurological symptoms. When more severe clinical symptoms are present, it is necessary to use imaging methods, such as magnetic resonance imaging (MRI), to confirm the diagnosis and establish the extent of the disease in order to determine proper treatment. There are several MRI changes which, based on clinicoradiological studies, are believed to be potential sources of pain and other clinical symptoms in DDS, including compression of the nerve root or spinal cord by disc herniations or osteophytes, recent ("active") disc herniation, Modic type 1 degenerative changes of the vertebral bodies, degenerative changes of the vertebral endplates (erosive intervertebral osteochondrosis), marked degenerative changes of the facet joints and ligamenta flava, degenerative spinal canal stenosis, degenerative spondylolisthesis, and Baastrup's disease. The authors analyzed the relationship of the MRI findings mentioned above with clinical symptoms of DDS, as well as the differentiation between DDS and nondegenerative diseases, which can manifest with similar clinical signs. The role of contrast-enhanced MRI and advanced MR techniques (e.g., high field MRI, functional MRI and MR spectroscopy) was also discussed. To establish an appropriate treatment for DDS, it is important to emphasize in the MRI report specific changes, which might be the cause of the pain and other clinical signs, as well as to rule out nondegenerative lesions, especially neoplasms, infections and rheumatoid disorders.
Topics: Humans; Intervertebral Disc Degeneration; Lumbar Vertebrae; Intervertebral Disc Displacement; Magnetic Resonance Imaging; Pain
PubMed: 37549011
DOI: 10.17219/acem/163357 -
Journal of Oral Biology and... 2023Temporomandibular disorders (TMDs) are a group of conditions that cause pain and dysfunction in the temporomandibular joint (TMJ) and muscles that control mandibular... (Review)
Review
Temporomandibular disorders (TMDs) are a group of conditions that cause pain and dysfunction in the temporomandibular joint (TMJ) and muscles that control mandibular movement. In most cases, the etiology is unclear and is considered multifactorial. Recent research suggests that some forms of TMD could be associated with specific TMJ morphological characteristics. This study aims to provide a review of the reported anatomical and degenerative morphological condylar characteristics of subjects with a clinical diagnosis of TMD as described with the use of CBCT imaging, as well as the detection of potential predisposing anatomical factors. This review was developed and reported in accordance with the PRISMA-ScR Checklist. A comprehensive search was performed in five databases. Reports were screened by two independent reviewers based on preselected inclusion and exclusion criteria. 45 studies were included in this review. The most frequently reported degenerative changes associated with TMD were condylar surface erosion, flattening, osteophytes, and sclerosis. Anatomical characteristics included a small condylar size and a posterior position of the condylar head in the TMJ. The anterosuperior area of the condylar head appears to be the most frequently affected. More studies are required to determine potential specific predisposing anatomical characteristics.
PubMed: 38028230
DOI: 10.1016/j.jobcr.2023.10.004 -
Journal of Cellular and Molecular... Feb 2024α-Solanine has been shown to exhibit anti-inflammatory and anti-tumour properties; however, its efficacy in treating osteoarthritis (OA) remains ambiguous. The study...
α-Solanine has been shown to exhibit anti-inflammatory and anti-tumour properties; however, its efficacy in treating osteoarthritis (OA) remains ambiguous. The study aimed to evaluate the therapeutic effects of α-solanine on OA development in a mouse OA model. The OA mice were subjected to varying concentrations of α-solanine, and various assessments were implemented to assess OA progression. We found that α-solanine significantly reduced osteophyte formation, subchondral sclerosis and OARSI score. And it decreased proteoglycan loss and calcification in articular cartilage. Specifically, α-solanine inhibited extracellular matrix degradation by downregulating collagen 10, matrix metalloproteinase 3 and 13, and upregulating collagen 2. Importantly, α-solanine reversed chondrocyte pyroptosis phenotype in articular cartilage of OA mice by inhibiting the elevated expressions of Caspase-1, Gsdmd and IL-1β, while also mitigating aberrant angiogenesis and sensory innervation in subchondral bone. Mechanistically, α-solanine notably hindered the early stages of OA progression by reducing I-κB phosphorylation and nuclear translocation of p65, thereby inactivating NF-κB signalling. Our findings demonstrate the capability of α-solanine to disrupt chondrocyte pyroptosis and sensory innervation, thereby improving osteoarthritic pathological progress by inhibiting NF-κB signalling. These results suggest that α-solanine could serve as a promising therapeutic agent for OA treatment.
Topics: Mice; Animals; NF-kappa B; Pyroptosis; Chondrocytes; Osteoarthritis; Disease Models, Animal; Collagen; Interleukin-1beta; Inflammation; Solanine
PubMed: 38345195
DOI: 10.1111/jcmm.18132 -
Chemico-biological Interactions Jan 2024Osteoarthritis (OA) is a heterogeneous disease that affects the entire joint. Its pathogenesis involves hypertrophy and hyperplasia of synovial cells and polarization...
Osteoarthritis (OA) is a heterogeneous disease that affects the entire joint. Its pathogenesis involves hypertrophy and hyperplasia of synovial cells and polarization infiltration of macrophages, in which macrophages, as a potential target, can delay the progression of the disease by improving the immune microenvironment in OA. To investigate the role and regulatory mechanism of Carveol in cartilage and synovial macrophage reprogramming and crosstalk during the development of OA. RAW264.7 mouse macrophage cell line was mainly used to stimulate macrophages to polarization towards M1 and M2 by LPS, IL4+IL13, respectively. Different concentrations of Carveol were given to intervene, and macrophage culture medium was collected to intervene mouse C57BL6J chondrocytes. ROS assay kit, western blotting, cellular immunofluorescence, scanning microscope and section histology were used to evaluate the effect of Carveol on anti-M1-polarization, M2-polarization promotion and cartilage protection. The mouse destabilization of medial meniscus (DMM) model was observed by micro-CT scan and histology. We found that CA could inhibit the increase of macrophage inflammation level under the intervention of LPS and promote the production of M2 anti-inflammatory substances under the intervention of IL-4+IL13. In addition, Carveol activated NRF2/HO-1/NQO1 pathway and enhanced ROS clearance in chondrocytes under the intervention of macrophage culture medium. The phosphorylation of I-κBα is inhibited, which further reduces the phosphorylation of P65 downstream of nuclear factor-κB (NF-κB) signaling pathway. In addition, Carveol inhibits mitogen activated protein kinase (MAPK) signaling molecules P-JNK, P-ERK and P-P38, and inhibits the production of inflammatory mediators. In vivo, Carveol can reduce osteophytes and bone spurs induced by DMM, reduce hypertrophy of synovial cells, reduce infiltration of macrophages, inhibit subchondral bone destruction, and reduce articular cartilage erosion. Our study suggests that synovial macrophages are potential targets for OA treatment, and Carveol is an effective candidate for OA treatment.
Topics: Mice; Animals; Lipopolysaccharides; Reactive Oxygen Species; Interleukin-13; Osteoarthritis; NF-kappa B; Disease Models, Animal; Macrophages; Hypertrophy; Chondrocytes
PubMed: 37967808
DOI: 10.1016/j.cbi.2023.110781 -
PloS One 2024Subacromial spurs are considered the one of the pathology underlying shoulder impingement syndrome. Furthermore, few studies have focused on the morphology of the...
BACKGROUND
Subacromial spurs are considered the one of the pathology underlying shoulder impingement syndrome. Furthermore, few studies have focused on the morphology of the subacromial spurs in normal Chinese people. This study aimed to study the spur distribution and to illustrate the morphology of spurs, which may help guide the extent of acromioplasty.
METHODS
A total of 93 normal individuals were enrolled, and both shoulders of all enrolled individuals were analyzed. The subjects were divided and classified into three different groups by ages: group I = 18-40 years, group II = 41-60 years, and group III ≥ 61 years. The osteophyte distribution, osteophyte area, subacromial surface area and osteophyte area/subacromial surface area ratio were measured and illustrated using Mimics and 3-matic software. The shape of the acromion was classified according to the Bigliani and Morrison classification system. The acromial angle was also classified. Then, the relationship between osteophytes, acromial classification and acromial angle was analyzed.
RESULTS
Type II (curved shape) was the most common type of acromion, and the hooked shape was a rare form. A significant increase in the left subacromial surface area in males was observed in group III compared with group I (P < 0.001) and group II (P = 0.004). The total spur/subacromial area ratio was significantly higher in group II than I. An obvious increase in the right subacromial area was observed in group III compared with group I (P = 0.004). Furthermore, there was a significant increase in the right spur area (P = 0.021) and total spur/subacromial area ratio (P = 0.006) in females in group II compared with group I. Fewer spurs were observed on the left than on the right side (p = 0.0482). One spur was most common among type II acromions (29/36) (80.56%) on the left side and the right side (34/52, 65.38%).
CONCLUSIONS
Spurs osteophytes are mainly distributed with an irregular shape and mostly run through the medial and lateral sides of the subacromial surface in normal subjects. The characteristics of subacromial spurs are so diverse that a surgeon must conduct subacromial decompression completely based on the morphology of individual spurs.
Topics: Adolescent; Adult; Female; Humans; Male; Young Adult; Acromion; Arthroplasty; East Asian People; Osteophyte; Shoulder Impingement Syndrome; Middle Aged
PubMed: 38547302
DOI: 10.1371/journal.pone.0301066