Effects of alendronate on cartilage lesions and micro-architecture deterioration of subchondral bone in patellofemoral osteoarthritic ovariectomized rats with patella-baja
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SUBMITTER: Bei M
PROVIDER: S-EPMC10962137 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Altered subchondral bone and articular cartilage interactions have been implicated in the pathogenesis of osteoarthritis (OA); however, the mechanisms remain unknown. Exosomes are membrane-derived vesicles that have recently been recognized as important mediators of intercellular communication. Herein, we investigated if OA subchondral bone derived exosomes alter transcriptional and bioenergetic signatures of chondrocytes. Exosomes were isolated and purified from osteoblasts of nonsclerotic or sclerotic zones of human OA subchondral bone and their role on the articular cartilage chondrocytes was evaluated by measuring the extent of extracellular matrix production, cellular bioenergetics, and the expression of chondrocyte activity associated marker genes. Exosomal microRNAs were analyzed using RNA sequencing and validated by quantitative real-time PCR and loss-of-function. In coculture studies, chondrocytes internalized OA sclerotic subchondral bone osteoblast derived exosomes and triggered catabolic gene expression and reduced chondrocyte-specific marker expression a phenomenon that is often observed in OA cartilage. RNA sequencing and miRNA profiling have identified miR-210-5p, which is highly enriched in OA sclerotic subchondral bone osteoblast exosomes, triggered the catabolic gene expression in articular cartilage chondrocytes. Importantly, we demonstrate that miR-210-5p suppresses the oxygen consumption rate of chondrocytes, altering their bioenergetic state that is often observed in OA conditions. These effects were markedly inhibited by the addition of a miR-210-5p inhibitor. Our study indicates that exosomes released by OA sclerotic subchondral bone osteoblasts plays a critical role in progression of cartilage degeneration and might be a potential target for therapeutic intervention in OA.
| S-EPMC7911822 | biostudies-literature
Project description:Early diagnosis of osteoarthritis (OA), before the onset of irreversible changes is crucial for understanding the disease process and identifying potential disease-modifying treatments from the earliest stage. OA is a whole joint disease and affects both cartilage and the underlying subchondral bone. However, spatial relationships between cartilage lesion severity (CLS) and microstructural changes in subchondral plate and trabecular bone remain elusive. Herein, we collected femoral heads from hip arthroplasty for primary osteoarthritis (n = 7) and femoral neck fracture (n = 6; non-OA controls) cases. Samples were regionally assessed for cartilage lesions by visual inspection using Outerbridge classification and entire femoral heads were micro-CT scanned. Scans of each femoral head were divided into 4 quadrants followed by morphometric analysis of subchondral plate and trabecular bone in each quadrant. Principal component analysis (PCA), a data reduction method, was employed to assess differences between OA and non-OA samples, and spatial relationship between CLS and subchondral bone changes. Mapping of the trabecular bone microstructure in OA patients with low CLS revealed trabecular organisation resembling non-OA patients, whereas clear differences were identifiable in subchondral plate architecture. The OA-related changes in subchondral plate architecture were summarised in the first principle component (PC1) which correlated with CLS in all quadrants, whilst by comparison such associations in trabecular bone were most prominent in the higher weight-bearing regions of the femoral head. Greater articular cartilage deterioration in OA was regionally-linked with lower BV/TV, TMD and thickness, and greater BS/BV and porosity in the subchondral plate; and with thinner, less separated trabeculae with greater TMD and BS/BV in the trabecular bone. Our findings suggest that impairment of subchondral bone microstructure in early stage of OA is more readily discernible in the cortical plate and that morphological characterisation of the femoral head bone microstructure may allow for earlier OA diagnosis and monitoring of progression.
| S-EPMC9035167 | biostudies-literature
Project description:ObjectiveThis study aimed to quantify the cartilage- and subchondral bone-related effects of low-dose and high-dose meloxicam treatment in the late phase of mono-iodoacetate-induced osteoarthritis of the stifle.MethodsThirty-four male Wistar rats received intra-articular injection of mono-iodoacetate to trigger osteoarthritis; 10 control animals (Grp Co) received saline. The mono-iodoacetate-injected rats were assigned to three groups and treated from week 4 to the end of week 7 with placebo (Grp P, n = 11), low-dose (GrpM Lo, 0.2 mg/kg, n = 12) or high-dose (GrpM Hi, 1 mg/kg, n = 11) meloxicam. After a period of 4 additional weeks (end of week 11) the animals were sacrificed, and the stifle joints were examined histologically and immunohistochemically for cyclooxygenase 2, in conformity with recommendations of the Osteoarthritis Research Society International. Serum cytokines IL-6, TNFα and IL-10 were measured at the end of weeks 3, 7, and 11.ResultsCompared with saline-treated controls, animals treated with mono-iodoacetate developed various degrees of osteoarthritis. The cartilage degeneration score and the total cartilage degeneration width were significantly lower in both the low-dose (p = 0.012 and p = 0.014) and high-dose (p = 0.003 and p = 0.006) meloxicam-treated groups than in the placebo group. In the subchondral bone, only high-dose meloxicam exerted a significant protective effect (p = 0.011). Low-grade Cox-2 expression observed in placebo-treated animals was abolished in both meloxicam groups. Increase with borderline significance of TNFα in GrpP from week 3 to week 7 (p = 0.049) and reduction of IL-6 in GrpM Lo from week 3 to week 11 (p = 0.044) were observed.ConclusionIn this rat model of osteoarthritis, both low-dose and high-dose meloxicam had a chondroprotective effect, and the high dose also protected against subchondral bone lesions. The results suggest a superior protection of the high-dose meloxicam arresting the low-grade inflammatory pathway accompanied by chronic cartilage deterioration.
| S-EPMC5391791 | biostudies-literature
Project description:Patella baja is a challenging pathologic condition that causes pain and functional restrictions and can even lead to premature osteoarthritis-even more so in cases of patella infera or cases associated with degeneration of the patellar tendon in which simple conservative treatment frequently is not resolutive. Several surgical options have been described for symptomatic patella baja: excision of the lower third of the patella, lengthening of the patellar tendon, reconstruction of the patellar tendon with allograft, and proximalization of the tibial tubercle. A combination of 2 or more of these treatments may be recommended in cases of significant patella baja. We present a simple and reproducible technique to address patella baja that combines a partial transposition of the tibial tubercle and patellar tendon lengthening using a subperiosteal patellar flap in continuity with the patellar tendon.
| S-EPMC6993128 | biostudies-literature
Project description:ObjectivesThis study aimed to determine the therapeutic effect of equol (EQ) on osteoporotic osteoarthritis (OP OA).Materials and methodsThirty-six 12-week-old female Sprague-Dawley rats were randomly divided into sham group, OP OA group, and EQ group (n=12). OP OA was induced by anterior cruciate ligament transection (ACLT) combined with ovariectomy (OVX). EQ was orally administrated (10 μg/g/day) after the operation for 12 weeks. The efficacy was evaluated by gross pathology and histopathologic evaluation. The underlying mechanism was investigated by immunohistochemical analysis, micro-computed tomography (micro-CT) scanning, and tartrate-resistant acid phosphatase (TRAP) staining.ResultsEQ effectively retarded cartilage degeneration, decreased the levels of matrix metalloproteinases-13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), nuclear factor-kappa B P65 (NF-κB P65) and caspase-3, and increased the levels of collagen type II (Col-II), Col-I, aggrecan (AGG), and inhibitor of NF-κB α (IκBα) in the cartilage. In addition, EQ increased bone mineral density, improved the microstructural parameters of the subchondral bone (SB), and decreased the number of osteoclasts.ConclusionEQ exerted a chondroprotective effect on OP OA in rats, associated with inhibition of the NF-κB signaling pathway and chondrocyte apoptosis. Furthermore, EQ showed an osteoprotective effect on SB via inhibiting osteoclastic activities.
| S-EPMC9588321 | biostudies-literature
Project description:Osteoarthritis (OA) is the most common joint disease, where articular cartilage degradation is often accompanied with sclerosis of the subchondral bone. However, the association between OA and tissue mineralization at the nanostructural level is currently not understood. In particular, it is technically challenging to study calcified cartilage, where relevant but poorly understood pathological processes such as tidemark multiplication and advancement occur. Here, we used state-of-the-art microfocus small-angle X-ray scattering with a 5-μm spatial resolution to determine the size and organization of the mineral crystals at the nanostructural level in human subchondral bone and calcified cartilage. Specimens with a wide spectrum of OA severities were acquired from both medial and lateral compartments of medial compartment knee OA patients (n = 15) and cadaver knees (n = 10). Opposing the common notion, we found that calcified cartilage has thicker and more mutually aligned mineral crystals than adjoining bone. In addition, we, for the first time, identified a well-defined layer of calcified cartilage associated with pathological tidemark multiplication, containing 0.32 nm thicker crystals compared to the rest of calcified cartilage. Finally, we found 0.2 nm thicker mineral crystals in both tissues of the lateral compartment in OA compared with healthy knees, indicating a loading-related disease process because the lateral compartment is typically less loaded in medial compartment knee OA. In summary, we report novel changes in mineral crystal thickness during OA. Our data suggest that unloading in the knee might be involved with the growth of mineral crystals, which is especially evident in the calcified cartilage. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
| S-EPMC9540032 | biostudies-literature
Project description:BackgroundElevated tibiofemoral and patellofemoral loading in children who exhibit crouch gait may contribute to skeletal deformities, pain, and cessation of walking ability. Surgical procedures used to treat crouch frequently correct knee extensor insufficiency by advancing the patella. However, there is little quantitative understanding of how the magnitudes of crouch and patellofemoral correction affect cartilage loading in gait.MethodsWe used a computational musculoskeletal model to simulate the gait of twenty typically developing children and fifteen cerebral palsy patients who exhibited mild, moderate, and severe crouch. For each walking posture, we assessed the influence of patella alta and baja on tibiofemoral and patellofemoral cartilage contact.ResultsTibiofemoral and patellofemoral contact pressures during the stance phase of normal gait averaged 2.2 and 1.0 MPa. Crouch gait increased pressure in both the tibofemoral (2.6-4.3 MPa) and patellofemoral (1.8-3.3 MPa) joints, while also shifting tibiofemoral contact to the posterior tibial plateau. For extended-knee postures, normal patellar positions (Insall-Salvatti ratio 0.8-1.2) concentrated contact on the middle third of the patellar cartilage. However, in flexed knee postures, both normal and baja patellar positions shifted pressure toward the superior edge of the patella. Moving the patella into alta restored pressure to the middle region of the patellar cartilage as crouch increased.ConclusionsThis work illustrates the potential to dramatically reduce tibiofemoral and patellofemoral cartilage loading by surgically correcting crouch gait, and highlights the interaction between patella position and knee posture in modulating the location of patellar contact during functional activities.
| S-EPMC5809194 | biostudies-literature
Project description:To determine the cross-sectional and longitudinal associations of patella alignment with cartilage relaxation and patients' self-reported symptoms. Thirty participants with isolated patellofemoral joint (PFJ) degeneration (six males, 53.7 ± 9.3 years) and 24 controls (12 males, 47.6 ± 10.7 years) were included. Magnetic resonance assessment was performed to provide grading of structural abnormalities, cartilage relaxation times, and patella alignment. Self-reported symptoms were assessed using the self-administrated knee injury and osteoarthritis outcome score (KOOS). All participants were examined at baseline and 3 years. Statistical parametric mapping and Pearson partial correlation were used to evaluate the associations between patella alignment with cartilage relaxation times and self-reported symptoms, respectively. The analyses were performed between baseline (cross-sectional) as well as the baseline against 3 years (longitudinal). Results indicated that patella height and patella flexion were associated with T1ρ and T2 relaxation times at baseline (percentages of voxels showing significant correlation [PSV] = 10.1%-24.8%; mean correlations [R] = 0.34-0.36; mean p = 0.015-0.026). Furthermore, greater patella lateral alignment, lateral tilt, and lateral spin were associated with longer T2 times at 3 years (PSV = 11.0%-14.4%, R = 0.39-0.44, p = 0.017-0.028). Last, a higher patella was associated with a lower KOOS at baseline and at 3 years (R = -0.33 to -0.35). The study suggests that patella malalignment is a risk factor for worsening cartilage health, informing clinicians of a better rehabilitation program that targets PFJ degeneration.
| S-EPMC9679042 | biostudies-literature
Project description:The mouse is an optimal model organism in which gene-environment interactions can be used to study the pathogenesis of osteoarthritis (OA). The gold standard for arthritis research in mice is based on histopathology and immunohistochemistry, which are labor-intensive, prone to sampling bias and technical variability, and limited in throughput. The aim of this study was to develop a new technique that assesses mouse cartilage by integrating quantitative volumetric imaging techniques.A novel mouse model of OA was generated by cruciate ligament transection (CLT) and evaluated by histopathology and immunohistochemistry. Knee joint specimens were then imaged using a new technique that combines high-resolution micro-computed tomography (micro-CT) and phase-contrast optics followed by quantitative analyses. A comparative analysis was also performed in a previously established mouse model of OA generated by destabilization of the medial meniscus (DMM).Phase-contrast micro-CT achieved cellular resolution of chondrocytes and quantitative assessment of parameters such as articular cartilage volume and surface area. In mouse models of OA generated by either CLT or DMM, we showed that phase-contrast micro-CT distinguished control and OA cartilage by providing quantitative measures with high reproducibility and minimal variability. Features of OA at the cellular or tissue level could also be observed in images generated by phase-contrast micro-CT.We established an imaging technology that comprehensively assessed and quantified the 2-dimensional and 3-dimensional changes of articular cartilage. Application of this technology will facilitate the rapid and high-throughput assessment of genetic and therapeutic models of OA in mice.
| S-EPMC3779602 | biostudies-literature
Project description:Bisphosphonates (BP) are considered a treatment option for osteoarthritis (OA) due to reduction of OA-induced microtrauma in the bone marrow, stabilization of subchondral bone (SB) layer and pain reduction. The effects of high-dose alendronate (ALN) treatment on SB and articular cartilage after destabilization of the medial meniscus (DMM) or Sham surgery of male C57Bl/6J mice were analyzed. We performed serum analysis; histology and immunohistochemistry to assess the severity of OA and a possible pain symptomatology. Subsequently, the ratio of bone volume to total volume (BV/TV), epiphyseal trabecular morphology and the bone mineral density (BMD) was analyzed by nanoCT. Serum analysis revealed a reduction of ADAMTS5 level. The histological evaluation displayed no protective effect of ALN-treatment on cartilage erosion. NanoCT-analysis of the medial epiphysis revealed an increase of BV/TV in ALN-treated mice. Only the DMM group had significantly higher SB volume accompanied by decreased subchondral bone surface. Furthermore Nano-CT analysis revealed an increase in trabecular density and number, a decreased BMD and reduced osteophyte formation in the ALN mice. ALN treatment affected bone micro-architecture by reducing osteophytosis with simultaneous increasing subchondral bone plate thickness, trabecular thickness and BMD. Accordingly, ALN cannot be considered as a potential treatment strategy in general, however in a subgroup of patients with high bone turnover in an early-stage of OA, ALN might be an option when applied during a restricted time frame.
| S-EPMC11500094 | biostudies-literature