Changes In Cartilage Research Articles

CHONDROCYTE-SPECIFIC KNOCKOUT OF PIEZO ION CHANNELS PROTECTS AGAINST POST-TRAUMATIC OSTEOARTHRITIS

Osteoarthritis (OA) is the leading cause of pain and disability worldwide and is characterized by the degenerative changes of articular cartilage. Joint loading is required for cartilage maintenance; however, hyper-physiologic loading is a risk factor for OA. Mechanosensitive ion channels Piezo1 and Piezo2 synergistically transduce hyper-physiologic compression of chondrocytes, leading to chondrocyte death and onset of OA. This injury response is inhibited by Piezo channel loss of function, however the mechanistic role of Piezo channels in vivo is unknown. We examined the hypothesis that deletion of Piezo in chondrocytes will protect mice from joint damage and pain-related behaviors following a surgical destabilization of the medial meniscus (DMM), investigating a key mechanistic and mechanobiological role of these channels in the pathogenesis of OA.Aggrecan-Cre Piezo1 and Piezo1/2 knockout mice ((Agc)1-CREERT2;Piezo1fl/flPiezo2fl/fl) were generated and given a 5-day Tamoxifen regimen at 12-weeks of age (n=6–12/group/sex). Cre-negative mice served as controls. At 16-weeks, mice received DMM surgery on the left knee. 12-weeks following DMM prior to sacrifice, activity and hyperalgesia were measured using spontaneous running wheels and a small animal algometer. Structural changes in bone, cartilage, and synovium were characterized using microCT, histology, and Modified Mankin Score criteria.Knockout of Piezo1/2 channels was chondroprotective in both sexes following DMM surgery as demonstrated by reduced Modified Mankin Score compared to control animals. Piezo1 KO was chondroprotective in only female mice, indicating a sexually dimorphic response. Piezo1 and Piezo1/2 KO was protective against pain in male mice, while females displayed no differences compared to controls. No changes were observed in bone morphology.Chondrocyte-specific Piezo1/2 knockout protects the knee joint from structural damage, hyperalgesia and functional deficits in a surgical model of PTOA in male and female mice, illustrating the importance of Piezo channels in response to injury in vivo. Future work aims to interrogate potential sexually dimorphic responses to cartilage damage and investigating Piezo2 KO mice.

Comparative evaluation of macro- and microscopic changes in rabbit, cattle, and pig auricular cartilage following exhumation after different postmortem intervals

The study evaluated and compared macro- and microscopic changes in the auricular cartilage of rabbits, cattle, and pigs following exhumation at different postmortem intervals (PMI). Eight samples corresponding to 0, 5, 10, 15, 20, 25, 30, and 150 days after exhumation were obtained from all rabbit ears, and twelve samples corresponding to 0, 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, and 150 days after exhumation were obtained from all cattle and pig ears. The weight loss of the rabbit ear samples remained higher than that of the cattle and pig ear samples at all PMIs. At 60 days, the average weight loss of cattle and pig ear samples did not differ significantly (p>0.05). The loss of area of the samples was similar among the three species at most PMIs (p>0.05). At 150 days, all cattle samples were completely decomposed, unlike the pig and rabbit samples. Microscopic analysis of the cartilage tinctorial affinity and loss of chondrocyte nuclei and tissue architecture demonstrated the worsening of postmortem changes over time, regardless of the animal species. Colonization by fungi and bacteria occurred earlier in the cattle and pig samples. The correlation of time with sample weight loss and cartilage thickness was strong, indicating the potential of these variables as parameters for PMI estimation. Therefore, postmortem examination of auricular cartilage can be used to estimate PMI.

Assessing the Correlation between the Radiological, Macroscopic and Histological Examination of Degenerative Changes of Articular Surfaces in Knee Osteoarthritis with Varus Deformity

Our study aims to compare the results of preoperative radiography and intraoperative visual assessment of the cartilage with histological assessment of joint surfaces of the medial and lateral compartments resected in patients during the total knee replacement. The cohort included 20 patients (9 men and 11 women) with the mean age of 66.6 (±7.0) years who met the inclusion criteria of the study. Degenerative changes of the knee joint seen on a preoperative weight-bearing anteroposterior X-ray were evaluated according to the Kellgren-Lawrence grading system separately for the medial and lateral compartment. Based on the visual appearance, the condition of articular surfaces was assessed using the International Cartilage Repair Society Score (ICRS Grade). The histological assessment of degenerative changes was conducted by a pathologist with the use of the Osteoarthritis Research Society International Osteoarthritis Cartilage Histopathology Assessment System based on six grades of articular cartilage degeneration. The mean degree of degenerative changes based on the radiological classification was assessed as 3.5 (±0.6) for the medial compartment and 2.1 (±0.4) for the lateral compartment. The visually assessed chondropathy according to the ICRS Grade was 3.7 (±0.6) for the medial femoral condyle and 1.8 (±1.0) for the lateral femoral condyle. The histological score obtained using the Osteoarthritis Research Society International Osteoarthritis Cartilage Histopathology Assessment was 4.9 (±1.1) for the medial femoral condyle and 2.4 (±0.7) for the lateral femoral condyle. In respect of the medial compartment, there was no statistically significant parametric correlation between the intraoperative visual assessment of the cartilage degeneration and the preoperative radiological grade r = 0.45. The histological assessment showed a statistically significant concordance both with the degree of chondropathy r = 0.76 and the radiological grade r = 0.64. In the lateral compartment, the parametric test showed a statistically significant concordance only between the radiological grade and the histological score r = 0.72. The correlation between the visual assessment of chondropathy and the radiological grade r = 0.27 as well as the histological score r = 0.24 was very low. In our cohort assessing the early degenerative changes of the lateral compartment as well as the more advanced degenerative changes of the medial compartment, the correlation between the intraoperative assessment of cartilage degeneration as a diagnostic method to examine the lateral compartment and the preoperative radiological grade was not confirmed. Our results failed to confirm a better reporting value of the visual cartilage degeneration assessment of the lateral compartment as against the preoperative X-ray. The space width without narrowing on an X-ray has no reporting value for this compartment in case of varus deformity. The results clearly indicate that the assessment of macroscopic appearance of the cartilage degeneration during arthroscopy does not necessarily guarantee good long-term clinical outcomes after high tibial osteotomy. The respective degrees of cartilage degeneration identified during the intraoperative visual assessment and the radiological grading of osteoarthritic changes did not correlate in either compartment. In the lateral compartment, the initial radiological and histological findings preceded the visually detectable cartilage changes. knee, cartilage, osteoarthritis, radiology, histology, arthroscopy, osteotomy.

Research progress of ultrasound in accurate evaluation of cartilage injury in osteoarthritis.

Osteoarthritis (OA) is a prevalent cause of joint algesia, loss of function, and disability in adults, with cartilage injury being its core pathological manifestation. Since cartilage damage is non-renewable, the treatment outcome in the middle and late stages of OA is unsatisfactory, which can be minimized by changing lifestyle and other treatment modalities if diagnosed and managed in the early stages, indicating the importance of early diagnosis and monitoring of cartilage injury. Ultrasound technology has been used for timely diagnosis and even cartilage injury treatment, which is convenient and safe for the patient owing to no radiation exposure. Studies have demonstrated the effectiveness of ultrasound and its various quantitative ultrasound parameters, like ultrasound roughness index (URI), reflection coefficient (R), apparent integrated backscatter (AIB), thickness, and ultrasound elastography, in the early and accurate assessment of OA cartilage pathological changes, including surface and internal tissue, hardness, and thickness. Although many challenges are faced in the clinical application of this technology in diagnosis, ultrasound and ultrasound-assisted techniques offer a lot of promise for detecting early cartilage damage in OA. In this review, we have discussed the evaluation of ultrasonic cartilage quantitative parameters for early pathological cartilage changes.

Deficiency of Cbfβ in articular cartilage leads to osteoarthritis-like phenotype through Hippo/Yap, TGFβ, and Wnt/β-catenin signaling pathways.

Osteoarthritis (OA) is the most prevalent degenerative joint disorder, causing physical impairments among the elderly. Core binding factor subunit β (Cbfβ) has a critical role in bone homeostasis and cartilage development. However, the function and mechanism of Cbfβ in articular cartilage and OA remains unclear. We found that Cbfβf/fAggrecan-CreERT mice with Cbfβ-deficiency in articular cartilage developed a spontaneous osteoarthritis-like phenotype with articular cartilage degradation. Immunofluorescence staining showed that Cbfβf/fAggrecan-CreERT mice exhibited a significant increase in the expression of articular cartilage degradation markers and inflammatory markers in the knee joints. RNA-sequencing analysis demonstrated that Cbfβ orchestrated Hippo/Yap, TGFβ/Smad, and Wnt/β-catenin signaling pathways in articular cartilage, and Cbfβ deficiency resulted in the abnormal expression of downstream genes involved in maintaining articular cartilage homeostasis. Immunofluorescence staining results showed Cbfβ deficiency significantly increased active β-catenin and TCF4 expression while reducing Yap, TGFβ1, and p-Smad 2/3 expression. Western blot and qPCR validated gene expression changes in hip articular cartilage of Cbfβ-deficient mice. Our results demonstrate that deficiency of Cbfβ in articular cartilage leads to an OA-like phenotype via affecting Hippo/Yap, TGFβ, and Wnt/β-catenin signaling pathways, disrupting articular cartilage homeostasis and leading to the pathological process of OA in mice. Our results indicate that targeting Cbfβ may be a potential therapeutic target for the design of novel and effective treatments for OA.

Acute responses and recovery in the femoral cartilage morphology following running and cool-down protocols.

This study compared the immediate effects of two common post-exercise cool-down methods to a control condition on subsequent morphologic change in femoral cartilage and vascular response in the posterior tibial artery after running. Sixteen healthy young males (23.6 ± 2.2 years, 172.8 ± 4.9 cm, 72.2 ± 7.1 kg) visited the laboratory during three separate sessions and performed 30-min of treadmill running (7.5 km/h for the initial 5-min, followed 8.5 km/h for 25-min). After running, participants experienced one of three 30-min cool-down protocols: active cool-down, cold application, or control (seated rest with their knee fully extended), in a counterbalanced order. Ultrasonographic assessments of femoral cartilage thickness (intercondylar, lateral, and medial) and posterior tibial artery blood flow were compared. To test condition effects over time, two-way analysis of variances and Tukey tests were used (p < 0.05) with Cohen's d effect sizes (ES). There was no condition by time interaction in femoral cartilage thickness (intercondylar: F30,705 = 0.91, p = 0.61; lateral: F30,705 = 1.24, p = 0.18; medial: F30,705 = 0.49, p = 0.99). Regardless of time (condition effect: F2,705 > 3.24, p < 0.04 for all tests), femoral cartilage in the cold application condition was thicker than the control condition (intercondylar: p = 0.01, ES = 0.16; lateral: p < 0.0001, ES = 0.24; medial: p = 0.04. ES = 0.16). Regardless of condition (time effect: F15,705 > 10.31, p < 0.0001 for all tests), femoral cartilage thickness was decreased after running (intercondylar: p < 0.0001, ES = 1.37; lateral: p < 0.0001, ES = 1.58; medial: p < 0.0001, ES = 0.81) and returned to baseline levels within 40-min (intercondylar: p = 0.09; lateral: p = 0.64; medial: p = 0.26). Blood flow volume was different (condition × time: F30,705 = 2.36, p < 0.0001) that running-induced blood flow volume was maintained for 30-min for the active cool-down condition (p < 0.0001, ES = 1.64), whereas it returned to baseline levels within 10-min for other conditions (cold application: p = 0.67; control: p = 0.62). Neither blood flow nor temperature had a significant impact on the recovery in femoral cartilage after running.

Morphohistological study of regeneration of knee joint cartilage defects in an experimental model under the influence of nuclear magnetic resonance therapy

Despite the variety of modern methods of treatment, the problem of hyaline cartilage regeneration is still relevant. Purpose of the study: to determine the effect of nuclear magnetic resonance therapy on the regenerative ability of simulated defects in the cartilage tissue of the knee joint in rats, to assess the dynamics of microscopic changes in articular cartilage in the main and control groups. The study was performed on 60 sex-mature rats. The defects were created in the area of the articular surfaces of the left knee joint – 30 defects in the main group and 30 defects in the control group. The right knee joint of both study groups was used as the norm. Medical (antibiotics, anti-inflammatory, analgesic) therapy was carried out for 3 days after the surgery. On the 4th day after surgery, rats of the main group were given nuclear magnetic resonance therapy for 60 minutes, for 7 days. After 7, 14, 21, 28 days after therapy, histological analysis of cartilage regenerate was performed. 28 days after the use of nuclear magnetic resonance therapy, the height of cartilage regenerate in rats was 82.12±8.89 μm in the intervention group and 56.34±7.82 μm in the control group. Cartilage regenerate in rats after nuclear magnetic resonance therapy was close to the structure of intact hyaline cartilage. However, complete regeneration did not occur, as evidenced by the smaller thickness of the articular cartilage compared to that in the right knee joint. In the control group, the formation of the regeneration had pronounced signs of dysregeneration. The cartilage tissue in the area of the defect, was predominantly fibrous in the nature with areas of necrosis. Nuclear magnetic resonance therapy contributes to the formation of articular cartilage in the defect – cartilage regenerate, which in its histological structure approaches hyaline cartilage.

Vibrational spectroscopy as a promising modality for diagnosing early osteoarthritis: a literature review

Background: Osteoarthritis (OA) is a joint disease caused by biological, chemical, and viscoelastic changes in the cartilage, synovium, subchondral bone, and synovial fluid. The current imaging techniques used to diagnose OA are frequently time-consuming, expensive, and damaging. Joint tissues have been examined using vibrational spectroscopy, and spectra of arthritic cartilage or subchondral bone in animals and people have revealed early chemical changes. This literature review aims to evaluate the role of vibrational spectroscopy in detecting early OA. Methods: Using the keywords "osteoarthritis," "imaging," "diagnostic," "spectroscopy," "vibrational spectroscopy," cartilage," and "synovial fluid," studies in online databases such as PubMed, the Cochrane Library, Wiley Online Library, and Google Scholar were searched for this review of the literature. After that, appropriate studies were conducted using a narrative synthesis analysis. Discussion: There are three types of vibrational spectroscopy, including near-infrared (NIR), infrared (IR), and Raman spectroscopy, which creates a vibrational spectrum from the vibrating of molecules or atomic groups brought on by electromagnetic radiation. Early OA can be identified by spectroscopic analysis of the synovial fluid, alterations in articular cartilage, and subchondral bone. The stretching and bending vibrations of C-H, N-H, and O-H bonds are visible in the NIR spectrum at wavelengths between 12,500 and 4000 cm-1. The transition between molecules' vibrational and rotational energy levels causes structural modifications in the 4000-400 cm-1 range, which are analyzed by IR spectroscopy. Raman spectroscopy uses the Raman scattering method to reflect the vibrational information between molecules. Conclusion: Vibrational spectroscopy is a promising modality for detecting early OA by analyzing synovial fluid spectrum, articular cartilage and subchondral bone changes.

The dual pro-inflammatory and bone-protective role of calcitonin gene-related peptide alpha in age-related osteoarthritis

BackgroundThe vasoactive neuropeptide calcitonin gene-related peptide alpha (αCGRP) enhances nociception in primary knee osteoarthritis (OA) and has been shown to disrupt cartilage and joint integrity in experimental rheumatoid arthritis (RA). Little is known about how αCGRP may alter articular structures in primary OA. We investigated whether αCGRP modulates local inflammation and concomitant cartilage and bone changes in a murine model of age-dependent OA.MethodsSixteen- to 18-month-old αCGRP-deficient mice (αCGRP−/−aged) were compared to, first, age-matched wild type (WTaged) and, second, young 4- to 5-month-old non-OA αCGRP-deficient (αCGRP−/−CTRL) and non-OA WT animals (WTCTRL). αCGRP levels were measured in serum. Knee and hip joint inflammation, cartilage degradation, and bone alterations were assessed by histology (OARSI histopathological grading score), gene expression analysis, and µ-computed tomography.ResultsWTaged mice exhibited elevated αCGRP serum levels compared to young WTCTRL animals. Marked signs of OA-induced cartilage destruction were seen in WTaged animals, while αCGRP−/−aged mice were mostly protected from this effect. Age-dependent OA was accompanied by an increased gene expression of pro-inflammatory Tnfa, Il1b, and Il6 and catabolic Mmp13, Adamts5, Ctsk, Tnfs11 (Rankl), and Cxcl12/Cxcr4 in WTaged but not in αCGRP−/−aged mice. αCGRP-deficiency however further aggravated subchondral bone sclerosis of the medial tibial plateau and accelerated bone loss in the epi- and metaphyseal trabecular tibial bone in age-dependent OA.ConclusionsSimilar to its function in experimental RA, αCGRP exerts a dual pro-inflammatory and bone-protective function in murine primary OA. Although anti-CGRP treatment was previously not successful in reducing pain in OA clinically, these data underline a crucial pathophysiological role of αCGRP in age-related OA.

Knee cartilage change on magnetic resonance imaging: Should we lump or split topographical regions? A 2-year study of data from the osteoarthritis initiative.

We challenge the paradigm that a simplistic approach evaluating anatomic regions (e.g., medial femur or tibia) is ideal for assessing articular cartilage loss on magnetic resonance (MR) imaging. We used a data-driven approach to explore whether specific topographical locations of knee cartilage loss may identify novel patterns of cartilage loss over time that current assessment strategies miss. We assessed 60 location-specific measures of articular cartilage on a sample of 99 knees with baseline and 24-month MR images from the Osteoarthritis Initiative, selected as a group with a high likelihood to change. We performed factor analyses of the change in these measures in two ways: (1) summing the measures to create one measure for each of the six anatomically regional-based summary (anatomic regions; e.g., medial tibia) and (2) treating each location separately for a total of 60 measures (location-specific measures). The first analysis produced three factors accounting for 66% of the variation in the articular cartilage changes that occur over 24 months of follow-up: (1) medial tibiofemoral, (2) medial and lateral patellar, and (3) lateral tibiofemoral. The second produced 20 factors accounting for 75% of the variance in cartilage changes. Twelve factors only involved one anatomic region. Five factors included locations from adjoining regions (defined by the first analysis; e.g., medial tibiofemoral). Three factors included articular cartilage loss from disparate locations. Novel patterns of cartilage loss occur within each anatomic region and across these regions, including in disparate regions. The traditional anatomic regional approach is simpler to implement and interpret but may obscure meaningful patterns of change.

Cationic tantalum oxide nanoparticle contrast agent for micro computed tomography reveals articular cartilage proteoglycan distribution and collagen architecture alterations

ObjectiveCationic tantalum oxide nanoparticles (Ta2O5-cNPs), as a newly introduced contrast agent for computed tomography (CT) of cartilage, offer quantitative evaluation of proteoglycan content and biomechanical properties. However, knowledge on the depth-wise impact of cartilage constituents on NP diffusion, particularly the influence of the collagen network, is lacking. In this study, we aim to establish the depth-dependent relationship between Ta2O5-cNP diffusion and cartilage constituents (proteoglycan content, collagen content and network architecture). MethodsOsteochondral samples (n = 30) were harvested from healthy equine stifle joints (N = 15) and the diffusion of 2.55 nm diameter cationic Ta2O5-cNPs into the cartilage was followed with µCT imaging for up to 96 hours. The diffusion-related parameters, Ta2O5-cNP maximum partition (Pmax) and diffusion time constant, were compared against biomechanical and depth-wise structural properties. Biomechanics were assessed using a stress-relaxation and sinusoidal loading protocols, whereas proteoglycan content, collagen content and collagen network architecture were determined using digital densitometry, Fourier-transform infrared spectroscopy and polarized light microscopy, respectively. ResultsThe Pmax correlates with the depth-wise distribution of proteoglycans (bulk Spearman’s ρ = 0.87, p < 0.001). More open collagen network architecture at the superficial zone enhances intake of Ta2O5-cNPs, but collagen content overall decreases the intake. The Pmax values correlate with the equilibrium modulus (ρ = 0.80, p < 0.001) of articular cartilage. ConclusionThis study establishes the feasibility of Ta2O5-cNPs for the precise and comprehensive identification of biomechanical and structural changes in articular cartilage via contrast-enhanced µCT.

Quantitative evaluation of warm acupuncture-moxibustion in improvement of cartilage damage in rabbits with early knee osteoarthritis based on MR T2 mapping.

To observe the application value of MR T2 mapping for evaluating the effect of warm acupuncture-moxibustion on articular cartilage degeneration, and to observe the relationship between T2 value and expression of matrix metalloproteinases (MMP)-1 and MMP-13 of chondrocytes in rabbits with early knee osteoarthritis (KOA). Thirty male New Zealand rabbits were randomly divided into blank control, KOA model and warm acupuncture-moxibustion groups, with 10 rabbits in each group. The early KOA model was established by right hind limb tubular plaster extension fixation method for 2 weeks. The rabbits of the warm acupuncture-moxibustion group received warm acupuncture-moxibustion stimulation at "Heding"(EX-LE2), "Neixiyan"(EX-LE4), "Waixiyan" (EX-LE5) and"Zusanli"(ST36) on the right hind limb for 15 min, once a day for 2 weeks. After intervention, MR T2 mapping of the right knee joint was performed in each group. The H.E. staining was used to evaluate the histopathological changes of cartilage, followed by giving a score according to the standards of Mankin scoring. The TUNEL method was used to analyze the apoptosis state of chondrocytes, and the positive expressions of MMP-1 and MMP-13 in the articular cartilage were detected by immunohistochemical staining. Compared with the blank control group, the Mankin score, chondrocyte apoptosis index, T2 value and the positive expressions of MMP-1 and MMP-13 in the cartilage tissue were significantly increased in the model group (P<0.01). Compared with the model group, the Mankin score, chondrocyte apoptosis index, T2 value and the positive expressions of MMP-1 and MMP-13 in the cartilage tissue were markedly decreased in the warm acupuncture-moxibustion group (P<0.01). The T2 value was positively correlated with the expression levels of MMP-1 and MMP-13 (P<0.01). H.E. staining showed disordered arrangement of chondrocytes and thinner cartilage layer in the model group, and a clear and relative ordered arrangement of chondrocyte in the warm acupuncture-moxibustion group. Warm acupuncture-moxibustion can reduce the T2 value of articular cartilage in early KOA rabbits, which is positively correlated with the decreased expression of MMP-1 and MMP-13 in the extracellular matrix of cartilage. The MR T2 mapping has certain value in evaluating the effect of warm acupuncture-moxibustion on KOA rabbits with early cartilage degeneration.

Runx1 alleviates osteoarthritis progression in aging mice

ABSTRACT With rates growing quickly with age, osteoarthritis (OA) is the most common cause of chronic disability in aging persons. The discomfort and reduced motion associated with osteoarthritis have a significant impact on quality of life, and there is no known solution. Runt-related transcription factor 1(Runx1) has been shown to play a protective role in the development of osteoarthritis by promoting chondrogenesis. We had created models of ageing mice with osteoarthritis by anterior cruciate ligament transection (ACLT) and analyzed the effects of intra-articular injection of adeno-associated virus/Runx1 (AAV/Runx1) on the models. The results showed that the AAV/Runx1-group maintained better articular cartilage integrity and retained more proteoglycan than the OA group after injection of AAV-Runx1. The markers related to pathological changes in cartilage were downregulated, while the markers related to physiological changes in cartilage were upregulated. This suggests that Runx1 may impede OA progression on the knee joint of ageing mice, potentially playing a protective role in OA and becoming a probable treatment target for osteoarthritis among ageing patients in the future.

Inotodiol ameliorates the progression of osteoarthritis: An in vitro and in vivo study

AbstractOsteoarthritis is a common chronic degenerative disease, of which the essence is the degenerative changes of bone and joint cartilage, involving damage in multiple structures such as bone, synovium and joints. In the mechanism of arthritis inflammation is closely related, and therefore the exploration to inhibit inflammatory mediators is crucial for the clinical prevention and treatment of osteoarthritis. Inotodiol is a lanostane triterpenoid isolated from Inonotus obliquus, which had been extensively reported to be an anti-inflammatory agent, but its effect on arthritis remains unknown. In this study, we firstly demonstrated that inotodiol significantly reduced IL-1β-induced chondrocyte injury and inhibited the release of inflammatory factors. At the same time, experiments in vivo showed that inotodiol could effectively improve the symptoms of joint injury in mice and reduce the area of cartilage destruction, indicating that inotodiol may be a potential therapeutic drug for osteoarthritis.

Postoperative quadriceps weakness and male sex are risk factors for patellofemoral articular cartilage lesions after anatomical anterior cruciate ligament reconstruction

PurposePatellofemoral (PF) compartment cartilage lesions are a frequent problem after anterior cruciate ligament (ACL) reconstruction. This study aimed to determine the factors that influence PF cartilage lesions after anatomical ACL reconstruction.MethodsThis study enrolled a total of 114 patients who did not manifest PF compartment cartilage lesions during anatomical ACL reconstruction and underwent second-look arthroscopy 18 months postoperatively. Arthroscopy using the International Cartilage Repair Society (ICRS) classification was used to assess cartilage lesions. The correlation between surgical findings, radiographic factors, and clinical factors and change of ICRS grade was analysed. Multivariate regression analysis was conducted to reveal the independent risk factors for PF cartilage lesions among patients’ demographic data and parameters that correlated with the change of ICRS grade in the correlation analyses.ResultsICRS grade changes in PF cartilage were significantly correlated with age, sex, quadriceps strength at 1 year postoperatively, hamstrings strength at pre- and 1 year postoperatively, and single leg hop test at 1 year postoperatively. However, no significant correlation was found between the time between injury and surgery, posterior tibial slope angle, pre- and postoperative Tegner activity scale, graft type, initial graft tension, meniscus injury, meniscus injury treatment, pre- and postoperative range of motion, anteroposterior laxity and preoperative quadriceps strength, and the change in ICRS grade. Multivariate regression analysis revealed male (P = 0.019) and quadriceps strength weakness at 1 year postoperatively (P = 0.009) as independent risk factors for PF cartilage lesions.ConclusionsQuadriceps strength weakness 1 year after ACL reconstruction and males were correlated with a new PF cartilage lesion after anatomical ACL reconstruction, with no significant correlation between bone-patellar tendon-bone autograft, initial graft tension, or extension deficit and new PF cartilage lesion. Rehabilitation that focuses on quadriceps strength after ACL reconstruction is recommended to prevent new PF cartilage lesions.Level of evidenceLevel IV.

MRI overestimates articular cartilage thickness and volume compared to synchrotron radiation phase-contrast imaging.

Accurate evaluation of morphological changes in articular cartilage are necessary for early detection of osteoarthritis (OA). 3T magnetic resonance imaging (MRI) has highly sensitive contrast resolution and is widely used clinically to detect OA. However, synchrotron radiation phase-contrast imaging computed tomography (SR-PCI) can also provide contrast to tissue interfaces that do not have sufficient absorption differences, with the added benefit of very high spatial resolution. Here, MRI was compared with SR-PCI for quantitative evaluation of human articular cartilage. Medial tibial condyles were harvested from non-OA donors and from OA patients receiving knee replacement surgery. Both imaging methods revealed that average cartilage thickness and cartilage volume were significantly reduced in the OA group, compared to the non-OA group. When comparing modalities, the superior resolution of SR-PCI enabled more precise mapping of the cartilage surface relative to MRI. As a result, MRI showed significantly higher average cartilage thickness and cartilage volume, compared to SR-PCI. These data highlight the potential for high-resolution imaging of articular cartilage using SR-PCI as a solution for early OA diagnosis. Recognizing current limitations of using a synchrotron for clinical imaging, we discuss its nascent utility for preclinical models, particularly longitudinal studies of live animal models of OA.

Age-Related Gene and Protein Expression in Mouse Mandibular Condyle Analyzed by Cap Analysis of Gene Expression and Immunohistochemistry

Introduction: Aging, an inevitable physiological process, leads to morphological and histological degenerative changes in the mandibular condylar cartilage (MCC); however, the molecular mechanism has not yet been elucidated, and little information is available on age-related factors. Therefore, this study was designed to identify age-related factors by investigating the age-related differentially expressed genes (DEGs) and localization of their translated protein expression in the mandibular condyle. Methods: Mandibular condyles were collected from 10- and 50-week-old mice. Total RNA was extracted from the samples and then analyzed using cap analysis of gene expression (CAGE) to identify age-related DEGs. Gene ontology (GO) enrichment analysis was performed to determine which biological processes were most affected by aging in terms of gene expression using Metascape. The mandibular condyle samples were processed for histology to investigate morphological changes caused by aging and for immunohistochemistry to localize the protein expression encoded by age-related genes identified with CAGE. Semi-quantitative immunohistochemistry was performed to assess age-related extracellular matrix (ECM) protein levels in the MCC. The histological sections were also used for Alcian blue histochemistry to detect glycosaminoglycans (GAGs). Results: GO enrichment analysis revealed that the genes related to “extracellular matrix organization,” including Acan, Col1a1, Col1a2, Col2a1, Mmp3, Mmp9, and Mmp13, were most differentially expressed in the aged mandibular condyle. Among these seven genes, Mmp3 was upregulated, and the others were downregulated with aging. Histological examination showed the age-related morphological and histological changes in the MCC. Immunohistochemical investigation showed the localization of matrix metalloproteinases (MMPs)-3, -9, and -13 and their substrate proteins, aggrecan, type I collagen, and type II collagen, in the mandibular condyle at 10 and 50 weeks, indicating different localizations between the young and the aged. In the aged MCC, semi-quantitative immunohistochemistry showed a significant decrease in the aggrecan protein level, and Alcian blue histochemistry showed a decrease in GAGs. Conclusion: MMP-3, MMP-9, and MMP-13 contribute to the remodeling of the ECM of the MCC and subchondral bone during aging by degrading ECM proteins at specific times and sites under the regulation of their production and secretion.

Effect of acupotomy on mitophagy mediated by PINK1/Parkin pathway in cartilage of rabbits with knee osteoarthritis

To observe the effect of acupotomy on mitophagy mediated by PINK1/Parkin pathway in cartilage of rabbits with knee osteoarthritis (KOA), so as to explore its mechanism in inhibiting cartilage damage. Twenty-one New Zealand rabbits were randomly divided into normal, model, and acupotomy groups, with 7 rabbits in each group. The KOA rabbit model was established by using the Videman method. Rabbits in the acupotomy group received regular acupotomy treatment around the knee joint nodules or tendons once a week for 3 consecutive weeks. HE staining and transmission electron microscopy were used to observe the morphological and ultrastructural changes in knee joint cartilage of rabbits. Flow cytometry was used to measure the mitochondrial membrane potential (Δψm) and reactive oxygen species (ROS) average fluorescence intensity in chondrocytes. Immunofluorescence was performed to detect the fluorescence intensity of LC3B, PINK1 and Parkin in cartilage tissue. Western blot was conducted to measure the protein expression levels of p62, LC3Ⅱ/Ⅰ, PINK1, and Parkin in cartilage tissue. Compared to the normal group, the model group showed fissures and tissue fibrosis on the surface of rabbit knee joint cartilages, loose distribution of chondrocytes, decreased autophagosomes, and abnormal mitochondrial morphology. The fluorescence intensity of LC3B, PINK1 and Parkin, the expression levels of LC3Ⅱ/Ⅰ, PINK1 and Parkin proteins in cartilage tissue were significantly decreased (P<0.01), while the percentage of chondrocytes with low Δψm, the average fluorescence intensity of ROS, and the expression of p62 protein in cartilage tissue were significantly increased (P<0.01). Compared to the model group, the acupotomy group showed no obvious defects on the surface of rabbit knee joint cartilage, relatively dense distribution of chondrocytes, increased autophagosomes, and relatively normal mitochondrial morphology. The fluorescence intensity of LC3B, PINK1 and Parkin, the expression of LC3Ⅱ/Ⅰ, PINK1 and Parkin proteins in cartilage tissue were significantly increased (P<0.01, P<0.05), while the percentage of chondrocytes with low Δψm, the average fluorescence intensity of ROS, and the expression of p62 protein in cartilage tissue were significantly decreased (P<0.01). Acupotomy may promote mitophagy by regulating the PINK1/Parkin pathway, thereby improving cartilage damage in rabbits with KOA.

Propolis as a Potential Therapeutic Agent to Counteract Age-Related Changes in Cartilage: An In Vivo Study.

Aging is intricately linked to chronic low-grade systemic inflammation, which plays a significant role in various age-related conditions, including osteoarthritis (OA). The aging process significantly influences the development of OA due to alterations in cartilage composition, reduced proteoglycan content, dysregulation of growth factor signaling, and heightened oxidative stress. Propolis, a natural product renowned for its potent antioxidant and anti-inflammatory properties, has the potential to mitigate age-induced changes in cartilage. The primary objective of this study was to rigorously assess the impact of in vivo propolis treatment on the histopathological characteristics of knee articular cartilage in senescent rats. This study involved a cohort of twenty male Sprague-Dawley rats, randomly allocated into four distinct groups for comparative analysis: YR (control group consisting of young rats), SR (senescent rats), SR-EEP (senescent rats treated with an ethanolic extract of propolis, EEP), and SR-V (senescent rats administered with a control vehicle). This study employed comprehensive histological and stereological analyses of knee articular cartilage. Propolis treatment exhibited a significant capacity to alleviate the severity of osteoarthritis, enhance the structural integrity of cartilage, and augment chondrocyte density. These promising findings underscore the potential of propolis as a compelling therapeutic agent to counteract age-related alterations in cartilage and, importantly, to potentially forestall the onset of osteoarthritis.

Effects of low-intensity exercise on spontaneously developed knee osteoarthritis in male senescence-accelerated mouse prone 8

BackgroundOsteoarthritis (OA) is a degenerative joint disease associated with aging, which often leads to joint stiffness and disability. Exercise is one of the most important non-pharmacological treatments and is prescribed as an indispensable treatment for OA. However, whether physical exercise is beneficial for preventing the progression of OA symptoms with age is poorly understood. We investigated the effects of exercise on spontaneously developed knee OA using male senescence-accelerated mouse prone 8 (SAMP8).MethodsTo examine age-related changes in the knee joints of SAMP8, knee articular cartilage changes, synovitis, knee joint flexion and extension angles, swelling, walking ability, and quadriceps muscle atrophy were analyzed at 3, 5, 7, and 9 months. SAMP8 were required to run at a speed of 10 m/min for 15 min/day from 7 to 9 months of age. The knee joint pathologies and symptoms of exercising and non-exercising mice were compared by histological, immunohistochemical, and morphometrical analyses.ResultsThe mice presented with various histological changes, including cartilage destruction, osteocyte formation, synovitis, declined joint angles, and swelling. Notably, medial and posterior cartilage destruction was more severe than that of the lateral and anterior cartilage. Knee joint angles were significantly correlated with the histological scores (modified Mankin and OARSI, osteophyte formation and synovial lining cell layer). Exercise did not attenuate cartilage degeneration in the medial and posterior tibial plateau, although the articular cartilage of the anterior and lateral tibial plateau and its histological scores was remained and significantly improved, respectively, by exercise. Exercise suppressed the age-related decline of collagen type II-positive areas in the remaining articular cartilage and improved the OA symptoms. Exercise reduced the expression of monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-α positive macrophages in the synovium.ConclusionThis study revealed that SAMP8 developed spontaneous knee OA with age, which resembled the disease symptoms in humans. Low-intensity exercise temporarily alleviated degeneration of the remaining cartilage, synovitis, and age-related decreases in knee flexion angle, stride length, and muscle atrophy in SAMP8. However, exercise during OA progression with age may cause mechanical stress that could be both beneficial and detrimental to joint health.