Healing Of Articular Cartilage Research Articles

Quantitative MRI Analysis of Patellofemoral Joint Cartilage Health 2 Years After Anterior Cruciate Ligament Reconstruction and Lateral Extra-Articular Tenodesis

Background: The addition of an iliotibial band–based lateral extra-articular tenodesis (LET) to anterior cruciate ligament (ACL) reconstruction (ACLR) has been shown to reduce failure rates. However, there are concerns as to the potential overconstraint of tibiofemoral kinematics that may increase the risk of cartilage degradation. To date, no clinical study has investigated the effect of LET on patellofemoral joint articular cartilage health. Hypothesis: It was hypothesized that at 2 years postoperatively, (1) the addition of LET at the time of ACLR would have no effect on cartilage health on magnetic resonance imaging (MRI), and (2) higher cartilage relaxation values would be associated with worse patient-reported and functional outcomes. Study Design: Cohort study; Level of evidence, 3. Methods: A subset of patients from the STABILITY 1 randomized controlled trial were included. All patients underwent primary ACLR with a hamstring autograft. Patients were randomized to either LET augmentation or not. Cartilage status in the patellofemoral joint between the ACLR group and ACLR+LET group was compared using 2-year postoperative quantitative MRI and the ACL osteoarthritis scores of both the surgical and the contralateral nonsurgical knees. Objective functional outcomes and patient-reported outcome measures (PROMs) were attained. Results: A total of 92 patients (43 patients in the ACLR group; mean age, 18.9 ± 3.2 years; 60.5% female; and 49 patients in the ACLR+LET group; mean age, 18.7 ± 3.2 years, 63.3% female) were included. No significant differences were seen in the mean values (ms) for adjusted T1ρ/T2 relaxation times in the medial patella (47.8/42.2 vs 47.3/43.2), central patella (45.5/42.5 vs 44.1/42.7), lateral patella (48.2/43.5 vs 47.3/43.0), medial trochlea (54.7/50.9 vs 56.4/50.9), central trochlea (53.3/51.1 vs 53.1/52.0), and lateral trochlea (54.9/52.1 vs 53.9/52.6) between the ACLR and ACLR+LET groups. No difference in overall ACL osteoarthritis scores was observed (P = .99). An increase in medial patellar T2 relaxation times was associated with a decreasing International Knee Documentation Committee score (P = .046), Knee injury and Osteoarthritis Outcome Score (KOOS) Symptoms subscale score (P = .01), and total KOOS (P = .01). Conclusion: There was no statistical difference in patellofemoral cartilage health between knees 2 years after primary ACLR with hamstring tendon autograft with or without LET. Statistically significant correlations were found between quantitative MRI relaxation times, functional outcome scores, and PROMs; however, the correlations were weak and the clinical significance is unknown. Registration: NCT02018354 (ClinicalTrials.gov identifier).

Human Adipose-derived Stem Cells Upregulate IGF-1 and Alleviate Osteoarthritis in a Two-stage Rabbit Osteoarthritis Model.

In recent years, it has been known that mesenchymal stem cells (MSCs) have the potential to treat osteoarthritis (OA). This study aimed to investigate the effects of intraarticular injection of human adipose-derived stem cells (hADSCs) in a new double-damage rabbit osteoarthritis model. The OA model was established surgically first by medial collateral ligament and anterior insertional ligament transection and medical meniscectomy, then by articular cartilage full-thickness defect. At six weeks following surgery, hADSCs were labeled with Enhanced Green Fluorescence Protein expressing lentivirus FG12 and injected into the knee joints. All rabbits were sacrificed at 4- and 8 weeks post-surgery. Assessments were carried out by macroscopic examination, immunohistochemistry staining, magnetic resonance imaging, qRT-PCR and ELISA analysis. At 4- and 8 weeks, hADSCs injection showed less cartilage loss, few fissures and few cracks, decreased volume of joint effusion and cartilage defect measured with MRI. Furthermore, ELISA and qRT-PCR methods showed that hADSCs treatment increased the level of IGF-1. Our data suggest that hADSC transplantation promotes articular cartilage healing in the double-damage rabbit osteoarthritis model, IGF-1 may play an essential role in the hADSC-based cartilage repair process. Transplantation of hADSCs may be suitable for clinical application in the treatment of osteoarthritis.

Estimation of Photon Path Length and Penetration Depth in Articular Cartilage Zonal Architecture Over the Therapeutic Window.

The key characteristics of light propagation are the average penetration depth, average maximum penetration depth, average maximum lateral spread, and average path length of photons. These parameters depend on tissue optical properties and, thus, on the pathological state of the tissue. Hence, they could provide diagnostic information on tissue integrity. This study investigates these parameters for articular cartilage which has a complex structure. We utilize Monte Carlo simulation to simulate photon trajectories in articular cartilage and estimate the average values of the light propagation parameters (penetration depth, maximum penetration depth, maximum lateral spread, and path length) in the spectral band of 400-1400 nm based on the optical properties of articular cartilage zonal layers and bulk tissue. Our findings suggest that photons in the visible band probe a localized small volume of articular cartilage superficial and middle zones, while those in the NIR band penetrate deeper into the tissue and have larger lateral spread. In addition, we demonstrate that a simple model of articular cartilage tissue, based on the optical properties of the bulk tissue, is capable to provide an accurate description of the light-tissue interaction in articular cartilage. The results indicate that as the photons in the spectral band of 400-1400 nm can reach the full depth of articular cartilage matrix, they can provide viable information on its pathological state. Therefore, diffuse optical spectroscopy holds significant importance for objectively assessing articular cartilage health. In this study, for the first time, we estimate the light propagation parameters in articular cartilage.

The effects of physiological and injurious hydrostatic pressure on murine ex vivo articular and growth plate cartilage explants: an RNAseq study.

Chondrocytes are continuously exposed to loads placed upon them. Physiological loads are pivotal to the maintenance of articular cartilage health, while abnormal loads contribute to pathological joint degradation. Similarly, the growth plate cartilage is subject to various loads during growth and development. Due to the high-water content of cartilage, hydrostatic pressure is considered one of the main biomechanical influencers on chondrocytes and has been shown to play an important role in the mechano-regulation of cartilage. Herein, we conducted RNAseq analysis of ex vivo hip cap (articular), and metatarsal (growth plate) cartilage cultures subjected to physiological (5 MPa) and injurious (50 MPa) hydrostatic pressure, using the Illumina platform (n = 4 replicates). Several hundreds of genes were shown to be differentially modulated by hydrostatic pressure, with the majority of these changes evidenced in hip cap cartilage cultures (375 significantly upregulated and 322 downregulated in 5 MPa versus control; 1022 upregulated and 724 downregulated in 50 MPa versus control). Conversely, fewer genes were differentially affected by hydrostatic pressure in the metatarsal cultures (5 significantly upregulated and 23 downregulated in 5 MPa versus control; 7 significantly upregulated and 19 downregulated in 50 MPa versus control). Using Gene Ontology annotations for Biological Processes, in the hip cap data we identified a number of pathways that were modulated by both physiological and injurious hydrostatic pressure. Pathways upregulated in response to 50 MPa versus control, included those involved in the generation of precursor metabolites and cellular respiration. Biological processes that were downregulated in this tissue included ossification, connective tissue development, and chondrocyte differentiation. Collectively our data highlights the divergent chondrocyte phenotypes in articular and growth plate cartilage. Further, we show that the magnitude of hydrostatic pressure application has distinct effects on gene expression and biological processes in hip cap cartilage explants. Finally, we identified differential expression of a number of genes that have previously been identified as osteoarthritis risk genes, including Ctsk, and Chadl. Together these data may provide potential genetic targets for future investigations in osteoarthritis research and novel therapeutics.

Atelocollagen Scaffold Enhances Cartilage Regeneration in Osteochondral Defects: A Study in Rabbits.

To enhance articular cartilage healing, microfractures (Mfx) and bone marrow aspirate concentrate (BMAC) are commonly used, and some form of scaffold is often used together to increase its efficacy. Herein, we compared the efficacy of atelocollagen scaffold to that of collagen scaffold when used with Mfx or BMAC on osteochondral defect of animal. This experiment was designed in two stages, and therapeutic effects of Mfx and BMAC were respectively evaluated when used with atelocollagen or collagen scaffold. Femoral condyle defects were artificially created in male New Zealand White rabbits, and in each stage, 12 rabbits were randomly allocated into three treatment groups: test group with additional atelocollagen scaffold, the positive control group with collagen scaffold, and the negative control group. Then, for 12weeks, macroscopic and histological evaluations were performed. At 12weeks, defects in the test group were fully regenerated with normal cartilage-like tissue, and were well integrated with the surrounding cartilage at both stages experiment, whereas defects in the control groups were not fully filled with regenerated tissue, and the tissue appeared as fibrous tissue. Histologically, the regenerated tissue in the test group showed a statistically significant improvement compared to the positive and negative control groups, achieving a similar structure as normal articular cartilage. The results showed that implantation of the atelocollagen scaffold enhanced cartilage regeneration following osteochondral defects in rabbits. This suggests that the atelocollagen scaffold can be used with Mfx or BMAC for effective regeneration of osteochondral defects.

Proteoglycans in Articular Cartilage and Their Contribution to Chondral Injury and Repair Mechanisms.

Proteoglycans are vital components of the extracellular matrix in articular cartilage, providing biomechanical properties crucial for its proper functioning. They are key players in chondral diseases, specifically in the degradation of the extracellular matrix. Evaluating proteoglycan molecules can serve as a biomarker for joint degradation in osteoarthritis patients, as well as assessing the quality of repaired tissue following different treatment strategies for chondral injuries. Despite ongoing research, understanding osteoarthritis and cartilage repair remains unclear, making the identification of key molecules essential for early diagnosis and effective treatment. This review offers an overview of proteoglycans as primary molecules in articular cartilage. It describes the various types of proteoglycans present in both healthy and damaged cartilage, highlighting their roles. Additionally, the review emphasizes the importance of assessing proteoglycans to evaluate the quality of repaired articular tissue. It concludes by providing a visual and narrative description of aggrecan distribution and presence in healthy cartilage. Proteoglycans, such as aggrecan, biglycan, decorin, perlecan, and versican, significantly contribute to maintaining the health of articular cartilage and the cartilage repair process. Therefore, studying these proteoglycans is vital for early diagnosis, evaluating the quality of repaired cartilage, and assessing treatment effectiveness.

Hydroquinone, an Environmental Pollutant, Affects Cartilage Homeostasis through the Activation of the Aryl Hydrocarbon Receptor Pathway.

Exposure to environmental pollutants has a proven detrimental impact on different aspects of human health. Increasing evidence has linked pollution to the degeneration of tissues in the joints, although through vastly uncharacterised mechanisms. We have previously shown that exposure to hydroquinone (HQ), a benzene metabolite that can be found in motor fuels and cigarette smoke, exacerbates synovial hypertrophy and oxidative stress in the synovium. To further understand the impact of the pollutant on joint health, here we investigated the effect of HQ on the articular cartilage. HQ exposure aggravated cartilage damage in rats in which inflammatory arthritis was induced by injection of Collagen type II. Cell viability, cell phenotypic changes and oxidative stress were quantified in primary bovine articular chondrocytes exposed to HQ in the presence or absence of IL-1β. HQ stimulation downregulated phenotypic markers genes SOX-9 and Col2a1, whereas it upregulated the expression of the catabolic enzymes MMP-3 and ADAMTS5 at the mRNA level. HQ also reduced proteoglycan content and promoted oxidative stress alone and in synergy with IL-1β. Finally, we showed that HQ-degenerative effects were mediated by the activation of the Aryl Hydrocarbon Receptor. Together, our findings describe the harmful effects of HQ on articular cartilage health, providing novel evidence surrounding the toxic mechanisms of environmental pollutants underlying the onset of articular diseases.

Harnessing Growth Factor Interactions to Optimize Articular Cartilage Repair.

The failure of cartilage healing is a major impediment to recovery from joint disease or trauma. Growth factors play a central role in cell function and have been proposed as potential therapeutic agents to promote cartilage repair. Decades of investigation have identified many growth factors that promote the formation of cartilage in vitro and in vivo. However, very few of these have progressed to human trials. A growth factor that robustly augments articular cartilage healing remains elusive. This is not surprising. Articular cartilage repair involves multiple cellular processes and it is unlikely that any single agent will be able to optimally regulate all of them. It is more likely that multiple regulatory molecules may be required to optimize the maintenance and restoration of articular cartilage. If this is the case, then interactions among growth factors may be expected to play a key role in determining their therapeutic value. This review explores the hypothesis that growth factor interactions could help optimize articular cartilage healing.

The Efficacy of High Tibial Osteotomy with or without Post-root Medial Meniscus Repair: A Systematic Review

Background: High tibial osteotomy (HTO) is a knee joint treatment modality for medial compartment arthritis, aiming to improve articular cartilage healing by shifting the lower limb’s axis. It is commonly used in younger patients with pain and active lifestyles, preventing advanced cartilage deterioration. Varus malalignment may often be accompanied with medial meniscus root tears. In recent years, meniscus root tears are often been repaired. However, the efficacy of medial meniscus repairs with high tibial in varus malalignment with medial meniscal tears remains a controversy. Purpose: The purpose is to study the functional outcomes of concurrent medial meniscus root repair with HTO versus HTO alone. Study design: Systematic review. Methods: According to Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, we searched PubMed, Embase, Web of Science, and the Cochrane Library databases for studies reporting the outcomes of medial meniscus posterior root tear (MMPRT) repair with HTO versus HTO alone and extracted data about characteristics of patients, clinical functional scores, and radiologic outcomes. One reviewer extracted data and 1 reviewer assessed the risk of bias and performed a synthesis of the evidence. Articles were eligible if they reported the functional outcome of HTO alone or HTO and MMPRT repair in patients of varus malalignment and medial meniscus root tears. Results: 6 studies with 264 patients were identified. Data from these studies were segregated in HTO only and HTO with medial meniscus repair group. The findings of this systematic review suggest that the outcomes of HTO with MMPHRR and of only HTO are not statistically significant, meaning that doing valgus osteotomy only in patients with varus knee and MMPHRT can give good results regardless of not repairing the meniscus. Conclusion: HTO with medial meniscus posterior horn root repair seems to have no significant improvement in the functional outcomes of the patient. However, long-term studies need to be performed. Keywords: High tibial osteotomy, medial meniscus, root repair, arthroscopy, varus malalignment, meniscus, root tear

Biochanin A protects against iron overload associated knee osteoarthritis via regulating iron levels and NRF2/System xc-/GPX4 axis

BackgroundIron homeostasis plays a positive role in articular cartilage health. Excessive iron or iron overload can induce oxidative stress damage in chondrocytes and ferroptosis cell death, advancing knee osteoarthritis (KOA). However, up to date, few effective agents treat iron overload-induced KOA (IOKOA). Chinese herbal medicine (CHM) provides abundant resources for drug selection to manage bone metabolic conditions, including osteoporosis. Biochanin A (BCA) is a novel bioactive multifunctional natural compound isolated from Huangqi, which has protective effects on bone loss. Nevertheless, the function and mechanism of BCA in treating IOKOA are still elusive. PurposeThis study seeks to uncover the potential therapeutic targets and mechanisms of BCA in the management of KOA with iron accumulation. MethodsIron dextrin (500 mg/kg) was intraperitoneally injected into mice to establish the iron overloaded mice model. OA was induced through surgery, and the progression was evaluated eight weeks following surgery. OA severity was evaluated with micro-CT and Safranin-O/Fast green staining in vivo. Iron deposition in the knee joint and synovium was assessed using Perl's Prussian blue staining. Ferric ammonium citrate (FAC) was then administered to primary chondrocytes to evaluate iron regulators mediated iron homeostasis. Toluidine blue staining was utilized to identify chondrocytes in vitro. The vitality of the cells was assessed using the CCK-8 test. The apoptosis rate of cells was measured using Annexin V-FITC/PI assay. The intracellular iron level was detected utilizing the calcein-AM test. Reactive oxygen species (ROS), lipid-ROS, and mitochondrial membrane potentiality were reflected via fluorescence density. Utilizing RT-qPCR and western blotting, the expression level was determined. ResultsMicro-CT and histological staining of knee joints showed greater cartilage degradation and higher iron buildup detected in iron-overloaded mice. BCA can reduce iron deposition and the severity of KOA. Toluidine blue staining and the CCK-8 assay indicated that BCA could rescue chondrocytes killed by iron. Cell apoptosis rates were increased due to iron overload but improved by BCA. Further, the intracellular content of iron, ROS, and lipid-ROS was increased with ferric ammonium citrate (FAC) treatment but restored after treatment with different concentrations of BCA. JC-1 staining revealed that BCA could reduce mitochondrial damage induced by iron overload. ConclusionIron overload was shown to promote chondrocyte ferroptosis in vivo and in vitro. Moreover, iron overload suppressed the expression of collagen II and induced MMP expression by catalyzing ROS generation with mitochondrial dysfunction. Our results showed that BCA could directly reduce intracellular iron concentration by inhibiting TfR1 and promoting FPN but also target the Nrf2/system xc-/GPX4 signaling pathway to scavenge free radicals and prevent lipid peroxidation. The results of this research indicate that BCA regulates iron homeostasis during the progression of osteoarthritis, which can open a new field of treatment for KOA.

Baseline knee extension may be associated with volumetric cartilage loss in the anterolateral tibia: data from the Osteoarthritis Initiative.

Animal studies suggest regional unloading of the knee due to flexion contracture (FC) results in cartilage loss in the anterior tibia. We looked for an association between the range of knee extension and articular cartilage thickness in the tibia of patients with knee OA, using quantitative MRI data from the OA Initiative. Baseline knee extension was measured using a goniometer. Cartilage thickness was measured using 3-Tesla coronal MRI images of the knee. The tibia articular cartilage was segmented into medial and lateral regions, then further divided into anterior, central and posterior subregions. We evaluated differences between participants with and without a knee FC and associations between knee extension and cartilage thickness, including percentage denudation of bones (0 mm thickness), using linear models. A total of 596 participants were included. Participants with a knee FC had a larger percentage of denuded bone in the anterolateral tibia vs participants without FC (2.2 ± 0.7% vs 0.4 ± 0.1%; P = 0.006), and knee extension was associated with anterolateral tibia denuded bone (r = 0.16, P < 0.001). After correcting for demographics, knee alignment, and OA severity, presence of FC and lost knee extension were associated with the percentage of denuded bone in the anterolateral tibia [β = 1.702 (0.634-2.770) and β = 0.261 (95% CI 0.134, 0.388), respectively]. While causation cannot be determined in this study, limitation in knee extension was statistically associated with the percentage of denuded bone in the anterolateral tibia. These novel data support that maintaining range of motion over the entire joint surface may help preserve articular cartilage health.

Force Platforms Can Accurately Predict Knee Kinetics Limb Asymmetry With Sit-to-stands During ACL Rehabilitation

Patients with ACL reconstruction presenting with lowered internal knee extensor moment during sports and mobility tasks exhibit markers of compromised articular cartilage health. Early detection and management of their knee extensor moment deficits during rehabilitation are paramount for risk reduction of future osteoarthritis. However, the technology to obtain knee moment data requires extensive training and financial resources. We seek a more affordable and less technically demanding clinical surrogate. PURPOSE: To determine if data obtained from two force platforms can accurately predict knee extensor moment asymmetry for diagnostic and training purposes early in rehabilitation. METHODS: The study is a retrospective analysis of 14 patients with unilateral ACL reconstruction who underwent motion analysis of a self-paced sit-to-stand from a 48 cm bench. All patients were engaged in rehabilitation at the time of testing. During testing, each foot was positioned on two lengthwise-aligned force platforms. Differences between limbs were tested with paired t-tests. Stepwise linear regression predicted limb symmetry in knee extensor moment with force platform variables of limb symmetry in peak aft forces (e.g. posterior), vertical forces, and differences in the fore-aft position of each leg's center of pressure. RESULTS: Patients presented with significant (p < 0.001) interlimb differences in knee extension moment (mean ± SD: involved = 0.62 ± 0.19 Nm/kg of body mass (BM); uninvolved = 1.06 ± 0.18), vertical ground reaction forces (p < 0.001, inv = 0.56 ± 0.05 BM; uninv = 0.66 ± 0.05), and aft forces (p < 0.001, inv = 0.024 ± 0.016 BM; uninv = 0.056 ± 0.021), and nearly significant for center of pressure position (p = 0.05, involved = 0.230 ± 0.04 m; uninvolved = 0.246 ± 0.026). The regression model explained a substantial portion of limb symmetry in knee extensor moment (R-squared = 0.887, p < 0.001) with all force platform variables contributing to the final model. CONCLUSIONS: The use of force platform parameters can strongly and accurately predict knee extensor moment asymmetry in patients with ACL reconstruction during rehabilitation. This prediction cluster is a promising and affordable alternative that may function as a surrogate measure of abnormal knee moment for retraining and improved clinical reasoning.

Effect of Mosaic Allograft Osteochondral Transplantation Combined with Corrective Osteotomy in Treating Osteochondral Lesions of the Talus on Ankle and Knee Joint Function and Lower Limb Alignment.

Objective To explore the effect of mosaic allograft osteochondral transplantation combined with corrective osteotomy in treating osteochondral lesions of the talus (OLT) on ankle and knee joint function and lower limb alignment. Methods One hundred and thirty-three OLT patients treated in our hospital between July 2015 and October 2019 were enrolled. Regarding the various surgical approaches, they were categorized into two groups, namely, A and B including 69 and 64 cases, respectively. The patients in group A were processed with mosaic allograft osteochondral transplantation combined with corrective osteotomy, and the patients in group B were processed with microfracture surgery. The Baird ankle function score and visual analog scale (VAS) were employed for evaluating the surgical efficacy and the degree of pain prior to and following surgery. The pre- and postoperative surgery-related indicators, Ankle Hindfoot Scale (AOOFAS), HSS score, lower limb alignment, and range of motion of the ankle were compared between the two groups, and changes in growth factor levels prior to and following processing were observed. Results Overall scores were better in group A than in group B (P < 0.05). The operation length was longer in group A, the amount of intraoperative blood loss was greater, and the length of hospitalization was less than in group B. The VAS score 48 hours after surgery was also lower (P < 0.05). Postoperative AOFAS scores in group A were better, and lower limb alignment was also less than in group B (P < 0.05). The postoperative HSS score did not differ significantly between the two groups (P > 0.05). The range of plantar flexion and dorsiflexion of the ankle joint was better in group A, and the levels of endothelial growth factor (VEGF), platelet-derived growth factor (PDG), and transforming growth factor β1 (TGF-β1) were lower than those in group B (P < 0.05). The occurrence of postoperative problems did not differ between the groups (P > 0.05). Conclusion Mosaic allograft osteochondral transplantation combined with corrective osteotomy has a high effective rate in the treatment of OLT, which can promote the healing of articular cartilage and the recovery of ankle joint functions, improve the range of motions of the ankle, and improve the lower limb alignment.

Infrared spectroscopy is suitable for objective assessment of articular cartilage health

ObjectiveTo evaluate the feasibility of Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy to detect cartilage degradation due to osteoarthritis and to validate the methodology with osteochondral human cartilage samples for future development towards clinical use. DesignCylindrical (d ​= ​4 ​mm) osteochondral samples (n ​= ​349) were prepared from nine human cadavers and measured with FTIR-ATR spectroscopy. Afterwards, the samples were assessed with Osteoarthritis Research Society International (OARSI) osteoarthritis cartilage histopathology assessment system and divided into two groups: 1) healthy (OARSI 0–2) and 2) osteoarthritic (OARSI 2.5–6). The classification was done with partial least squares discriminant analysis model utilizing cross-model validation. Receiver operating characteristics curve analysis was performed and the area under curve (AUC) was calculated. ResultsFor all samples combined, classification accuracy was 73% with AUC of 0.79. Femoral samples had accuracy of 74% and AUC of 0.77, while tibial samples had accuracy of 66%, and AUC of 0.74. Patellar samples had accuracy of 84% and AUC of 0.91. ConclusionsThe results indicate that FTIR-ATR spectroscopy can differentiate between healthy and osteoarthritic femoral, tibial and patellar human tissue. If combined with a fiber optic probe, FTIR-ATR spectroscopy could provide additional objective intraoperative information during arthroscopic surgeries, which could improve clinical outcomes.

Blood flow Restriction training After patellar INStability (BRAINS Trial)

BackgroundPatellar instability is a common and understudied condition that disproportionally affects athletes and military personnel. The rate of post-traumatic osteoarthritis that develops following a patellar dislocation can be up to 50% of individuals 5–15 years after injury. Conservative treatment is the standard of care for patellar instability however, there are no evidence-informed rehabilitation guidelines in the scientific literature. The purpose of this study is to assess the effectiveness of blood-flow restriction training (BFRT) for patellar instability. Our hypotheses are that this strategy will improve patient-reported outcomes and accelerate restoration of symmetric strength and knee biomechanics necessary to safely return to activity.Methods/designThis is a parallel-group, superiority, randomized, double-blinded, placebo-controlled clinical trial at the University of Kentucky, sports medicine clinic that aims to recruit 78 patients with acute patellar dislocations randomly allocated into two groups: (1) sham BFRT and (2) BFRT. Both groups will receive the current standard of care physical therapy 3 times per week for up to 9 weeks. Physical therapy sessions will consist of typical standard of care treatment followed by BFRT or sham BFRT. Primary outcomes include the Norwich Patellar Instability Scale, quadriceps strength, and imaging and biochemical biomarkers of cartilage degradation.DiscussionThe current standard of care for non-operative treatment of patellar instability is highly variable does not adequately address the mechanisms necessary to restore lower extremity function and protect the long-term health of articular cartilage following injury. This proposed novel intervention strategy uses an easily implementable therapy to evaluate if BFRT significantly improves patient-reported outcomes, function, and joint health over the first year of recovery.Trial registrationBlood Flow Restriction Training, Aspiration, and Intraarticular Normal Saline (BRAINS) NCT04554212. Registered on 18 September 2020.

Therapeutic Role of Platelet Rich Plasma in Formaldehyde-Induced Arthritis in Adult Male Albino Rats

Abstract Introduction Osteoarthritis (OA) is a common health problem. Platelet-rich plasma (PRP) has been recognized to enhance articular cartilage metabolism. Aim of the work the study was designed to investigate the influence of PRP on cartilage healing after induction of arthritis. Material and methods Forty two adult male albino rats were used in this study. The rats were randomly divided into three groups: Group I (n = 18): the control group (Ia, Ib &amp; Ic) Ib &amp; Ic were injected intra-articularly with saline and left for 3 and 6 weeks. Group II (n = 12): arthritic group, in which osteoarthritis was induced by injection of 0.02ml 5% formaldehyde once in the right knee joints, left without treatment, and were sacrificed after three weeks (IIa) or after six weeks (IIb). Group III(n = 12): arthritis was induced as group II, one week later, the rats were intra-articularly injected with single dose of 0.3ml PRP in the same joint then were sacrificed three weeks (IIIa) or six weeks (IIIb) after formaldehyde injection. At the end of the study the right knee joints were taken, decalcified then processed for paraffin sections to be examined by light microscope using H&amp;E, toluidine blue and Masson’s trichrome (MTC) stains. Immunohistochemistry for caspase-3 enzyme was done to demonstrate apoptotic chondrocytes. Morphometric study was conducted to measure the thickness of the non-calcified cartilage, count the chondrocytes and synovial membrane inflammatory cells and Mankin's score. Then statistical analysis was done. Results The arthritic groups revealed irregular surface of the articular cartilage, loss of the articular matrix and bone eburnation. Moreover, there was apparent hypocellularity and disorganization of the chondrocytes. Osteoclasts and osteoblasts were seen invading the osteochondral junction. MTC stained sections of the synovial membrane showed deposition of thick collagen bundles with heavy inflammatory cell infiltrate and numerous blood vessels. The affinity of the articular cartilage to toluidine blue stain was apparently decreased while caspase-3 immunoreactivity was apparent in many chondrocytes .Group IIIa demonstrated almost similar histological findings as the control group; regular articular cartilage surface with regularly arranged chondrocytes in the different cartilage zones. Synovial membrane illustrated minimal inflammatory cell infiltrate with thin collagen bundles and small blood vessels in MTC stained sections. There was high affinity of the articular cartilage to the toluidine blue stain and few chondrocytes showed positive caspase-3 immunoreactivity. Group IIIb revealed continuous surface of the articular cartilage, yet with minimal fibrillation in some areas. Osteoblasts and osteoclasts were seen invading the calcified cartilage. Synovial membrane showed deposition of dense collagen bundles with some inflammatory cell infiltrate. Toluidine blue sections revealed decreased articular cartilage affinity to the stain while caspase-3 immunoreactivity was evident in many chondrocytes. The morphometric results and statistical analysis confirmed the histological findings. Conclusion Intra-articular injection of PRP demonstrated advantageous role on articular cartilage healing, however, these effects appeared to be transient. So the need of multiple injections of PRP has to be considered in cases of OA.

Association of Jump-Landing Biomechanics With Tibiofemoral Articular Cartilage Composition 12 Months After ACL Reconstruction.

Background:Excessively high joint loading during dynamic movements may negatively influence articular cartilage health and contribute to the development of posttraumatic osteoarthritis after anterior cruciate ligament reconstruction (ACLR). Little is known regarding the link between aberrant jump-landing biomechanics and articular cartilage health after ACLR.Purpose/Hypothesis:The purpose of this study was to determine the associations between jump-landing biomechanics and tibiofemoral articular cartilage composition measured using T1ρ magnetic resonance imaging (MRI) relaxation times 12 months postoperatively. We hypothesized that individuals who demonstrate alterations in jump-landing biomechanics, commonly observed after ACLR, would have longer T1ρ MRI relaxation times (longer T1ρ relaxation times associated with less proteoglycan density).Study Design:Cross-sectional study; Level of evidence, 3.Methods:A total of 27 individuals with unilateral ACLR participated in this cross-sectional study. Jump-landing biomechanics (peak vertical ground-reaction force [vGRF], peak internal knee extension moment [KEM], peak internal knee adduction moment [KAM]) and T1ρ MRI were collected 12 months postoperatively. Mean T1ρ relaxation times for the entire weightbearing medial femoral condyle, lateral femoral condyle (global LFC), medial tibial condyle, and lateral tibial condyle (global LTC) were calculated bilaterally. Global regions of interest were further subsectioned into posterior, central, and anterior regions of interest. All T1ρ relaxation times in the ACLR limb were normalized to the uninjured contralateral limb. Linear regressions were used to determine associations between T1ρ relaxation times and biomechanics after accounting for meniscal/chondral injury.Results:Lower ACLR limb KEM was associated with longer T1ρ relaxation times for the global LTC (ΔR 2 = 0.24; P = .02), posterior LTC (ΔR 2 = 0.21; P = .03), and anterior LTC (ΔR 2 = 0.18; P = .04). Greater ACLR limb peak vGRF was associated with longer T1ρ relaxation times for the global LFC (ΔR 2 = 0.20; P = .02) and central LFC (ΔR 2 = 0.15; P = .05). Peak KAM was not associated with T1ρ outcomes.Conclusion:At 12 months postoperatively, lower peak KEM and greater peak vGRF during jump landing were related to longer T1ρ relaxation times, suggesting worse articular cartilage composition.

Protective Effect of SIRT1 Activator on the Knee With Osteoarthritis.

Osteoarthritis (OA), one of the most common chronic musculoskeletal disorders, is deemed to be correlated with aging. The SIRT1 activator, resveratrol, acts as a crucial regulator of aging and may have a potential therapeutic effect on OA. Rabbit OA models were established through destabilized medial meniscus surgery. A total of 40 healthy male New Zealand rabbits were divided into five groups: control group (sham operation), OA group, as well as low dose (LD), middle dose (MD), and high dose (HD) resveratrol-treated OA groups. 6 weeks after operation, 0.8 ml of normal saline was injected into the knee joints every other day in the control and OA groups, and 0.8 ml of 5, 10, and 15 μmol/L resveratrol was injected into the knee joints every other day in the LD, MD, and HD group, respectively. The rabbits were sacrificed 2 weeks after medication, and the articular cartilage of the knee joint was collected for Micro-CT, histology and Western blot analysis. Obvious articular cartilage lesion and joint space narrowing were detected in the OA group. Compared with the OA group, less osteoarthritic changes were observed in the MD and HD groups. The MD and HD groups had significantly lower bone volume fraction, trabecular number and Mankin scores than the LD and OA groups (p < 0.05). No significant difference was found between the OA and LD groups (p > 0.05). The expressions of SIRT1 and p53 detected by western blot were consistent with the aforementioned findings. Therefore, resveratrol can activate the SIRT1 gene to play a protective role in the OA process by inhibiting chondrocyte apoptosis, trabecular bone number increasing of the subchondral bone, as well as elevation of bone density. It demonstrated the importance of SIRT1 in maintaining articular cartilage health and provided a promising therapeutic intervention in the treatment of OA.

Loading during midstance of gait is associated with tibiofemoral articular cartilage composition following anterior cruciate ligament reconstruction

Loading during midstance of gait is associated with tibiofemoral articular cartilage composition following anterior cruciate ligament reconstruction

Mechanosensitive blood markers and their interrelation in patients with medial compartment knee osteoarthritis

Purpose: The response of biomarkers of joint metabolism to mechanical stimuli in healthy and pathological conditions has attracted increasing attention in recent years. The main motivation for research on this interrelationship is improving the understanding of the etiology and pathomechanics of degenerative joint diseases such as osteoarthritis (OA), identifying potential biomarkers for early OA, developing frameworks for clinical trials in chondrogenic drug development, and understanding the effects of obesity, immobilization, exercise and space flight on articular cartilage health.