Changes In Articular Cartilage Research Articles

Changes of bone and articular cartilage in broilers with femoral head necrosis

Femoral head necrosis (FHN) in broilers is a common leg disorder in intensive poultry farming, giving rise to poor animal health and welfare. Abnormal mechanical stress in the hip joint is a risk factor for FHN, and articular cartilage is attracting increasing attention as a cushion and lubrication structure for the joint. In the present study, broilers aged 3 to 4 wk with FHN were divided into femoral head separation (FHS) and femoral head separation with growth plate lacerations (FHSL) groups, with normal broilers as control. The features of the hip joint, bone, and cartilage were assessed in FHN progression using devices including computed tomography (CT), atomic force microscope (AFM), and transmission electron microscopy (TEM). Broilers with FHN demonstrated decreased bone mechanical properties, narrow joint space, and thickened femoral head stellate structures. Notably, abnormal cartilage morphology was observed in FHN-affected broilers, characterized by increased cartilage thickness and rough cartilage surfaces. In addition, as FHN developed, cartilage surface friction and friction coefficient dramatically increased, while cartilage modulus and stiffness decreased. The ultramicro-damage occurred in chondrocytes and the extracellular matrix (ECM) of cartilage. Cell disintegration, abnormal mitochondrial accumulation, and oxidative stress damage were observed in chondrocytes. A notable decline in cartilage collagen content was observed in ECM during the initial stages of FHN, accompanied by a pronounced reduction in collagen fiber diameter and proteoglycan content as FHN progressed. Furthermore, the noticeable loosening of the collagen fiber structure and the appearance of type I collagen were noted in cartilage. In conclusion, there was a progressive decrease in bone quality and multifaceted damage of cartilage in the femoral head, which was closely linked to the severity of FHN in broilers.

Measurement of T1ρ dispersion with compressed sensing and magnetization prepared radial balanced steady-state free precessionin spontaneous human osteoarthritis.

To assess the potential for accelerating continuous-wave (CW) T1ρ dispersion measurement with compressed sensing approach via studying the effect that the data reduction has on the ability to detect differences between intact and degenerated articular cartilage with different spin-lock amplitudes and to assess quantitative bias due to acceleration. Osteochondral plugs (n = 27, 4 mm diameter) from femur (n = 14) and tibia (n = 13) regions from human cadaver knee joints were obtained from commercial biobank (Science Care, USA) under Ethical permission 134/2015. MRI of specimens was performed at 9.4T with magnetization prepared radial balanced SSFP (bSSFP) readout sequence, and the CWT1ρ relaxation time maps were computed from the measured data. The relaxation time maps were evaluated in the cartilage zones for different acceleration factors. For reference, Osteoarthritis Research Society International (OARSI) grading and biomechanical measurements were performed and correlated with the MRI findings. Four-fold acceleration of CWT1ρ dispersion measurement by compressed sensing approach was feasible without meaningful loss in the sensitivity to osteoarthritic (OA) changes within the articular cartilage. Differences were significant between intact and OA groups in the superficial and transitional zones, and CWT1ρ correlated moderately with the reference measurements (0.3 < r < 0.7). CWT1ρ was able to differentiate between intact and OA cartilage even with four-fold acceleration. This indicates that acceleration of CWT1ρ dispersion measurement by compressed sensing approach is feasible with negligible loss in the sensitivity to osteoarthritic changes in articular cartilage.

A brief review of current treatment options for osteoarthritis including disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics.

Osteoarthritis (OA) is a chronic disorder caused by degenerative changes in articular cartilage, which are mainly manifests as degeneration of cartilage, subchondral bone remodeling, as well as synovial inflammation. Over the next few decades, OA and its burden will continue to increase worldwide, posing a major public health challenge for the foreseeable future. Treatment for OA includes non-pharmacological, pharmacological, and surgical treatments. Existing conservative treatments and joint surgery can only alleviate the symptoms and cannot be cured, so new therapies for OA are urgently needed. Since advances in the understanding of OA pathophysiology, researchers have identified some potential therapeutic targets against degeneration of cartilage, subchondral bone remodeling and synovial inflammation, enabling development of the disease-modifying OA drugs (DMOADs). Additionally, a number of new technologies are also being investigated for treating OA, such as RNA interference (RNAi), CRISPR/Cas9 and PROTAC. The goal of this review is to describe the current development status of DMOADs and to discuss the potential of emerging therapeutic approaches for treating OA, thus providing a reference for OA treatments.

Inflammatory diseases causing joint and bone destruction: rheumatoid arthritis and hemophilic arthropathy

AbstractVarious diseases and conditions cause joint disorders. Osteoarthritis (OA) is characterized by the degeneration of articular cartilage, synovitis, and anabolic changes in surrounding bone tissues. In contrast, rheumatoid arthritis (RA) and hemophilic arthropathy (HA) display marked destruction of bone tissues caused by synovitis. RA is a representative autoimmune disease. The primary tissue of RA pathogenesis is the synovial membrane and involves various immune cells that produce catabolic cytokines and enzymes. Hemophilia is a genetic disorder caused by a deficiency in blood clotting factors. Recurrent intra-articular bleeding leads to chronic synovitis through excessive iron deposition and results in the destruction of affected joints. Although the triggers for these two joint diseases are completely different, many cytokines and enzymes are common in the pathogenesis of both RA and HA. This review focuses on the similarities between joint and bone destruction in RA and HA. The insights may be useful in developing better treatments for hemophilia patients with arthropathy and osteoporosis by leveraging advanced therapeutics for RA.

Anterior cruciate ligament injury and age affect knee cartilage T2 but not thickness

ObjectiveTo investigate the effect of unilateral anterior cruciate ligament (ACL) injury on cartilage thickness and composition, specifically laminar transverse relaxation time (T2) by magnetic resonance imaging (MRI), in younger and older participants and to compare within-person side differences in these parameters between ACL-injured and healthy controls. DesignQuantitative double-echo steady-state (qDESS) 3 Tesla MRI-sequences were acquired in both knees of 85 participants in four groups: 20–30 years: healthy, HEA20–30, n=24; ACL-injured, ACL20–30, n=23; 40–60 years: healthy, HEA40–60, n=24; ACL-injured, ACL40–60, n=14 (ACL injury 2–10 years prior to study inclusion). Weight-bearing femorotibial cartilages were manually segmented; cartilage T2 and thickness were computed using custom software. Mean and side difference in subregional cartilage thickness, superficial and deep cartilage T2 were compared within and between groups using non-parametric statistics. ResultsCartilage thickness did not differ within or between groups. Only the side difference in medial femorotibial cartilage thickness was greater in ACL20–30 than in HEA20–30. Deep zone T2 was longer in the ACL-injured than in the contralateral uninjured knees and than in healthy controls, especially in the lateral compartment. Most ACL-injured participants had side differences in femorotibial deep zone T2 above the threshold derived from controls. ConclusionIn the ACL-injured knee, early compositional differences in femorotibial cartilage (T2) appear to occur in the deep zone and precede cartilage thickness loss. These results suggest that monitoring laminar T2 after ACL injury may be useful in the diagnosing and monitoring early articular cartilage changes.

Prg4-Expressing Chondroprogenitor Cells in the Superficial Zone of Articular Cartilage.

Joint-resident chondrogenic precursor cells have become a significant therapeutic option due to the lack of regenerative capacity in articular cartilage. Progenitor cells are located in the superficial zone of the articular cartilage, producing lubricin/Prg4 to decrease friction of cartilage surfaces during joint movement. Prg4-positive progenitors are crucial in maintaining the joint's structure and functionality. The disappearance of progenitor cells leads to changes in articular hyaline cartilage over time, subchondral bone abnormalities, and the formation of ectopic ossification. Genetic labeling cell technology has been the main tool used to characterize Prg4-expressing progenitor cells of articular cartilage in vivo through drug injection at different time points. This technology allows for the determination of the origin of progenitor cells and the tracking of their progeny during joint development and cartilage damage. We endeavored to highlight the currently known information about the Prg4-producing cell population in the joint to underline the significance of the role of these cells in the development of articular cartilage and its homeostasis. This review focuses on superficial progenitors in the joint, how they contribute to postnatal articular cartilage formation, their capacity for regeneration, and the consequences of Prg4 deficiency in these cells. We have accumulated information about the Prg4+ cell population of articular cartilage obtained through various elegantly designed experiments using transgenic technologies to identify potential opportunities for further research.

Micro-computed tomography reveals high-density mineralised protrusions and microstructural lesions in equine stifle joint articular cartilage.

Stifle osteoarthritis (OA) lesions are most common in the medial femorotibial (MFT) compartment. Their characterisation and mapping will inform equine veterinarians towards an accurate diagnosis of OA. Investigate and map micro-CT (μCT) changes in the hyaline articular cartilage (HAC) in the medial femoral condyle (MFC) and medial tibial plateau (MTP). Ex vivo cadaveric. Stifles (n = 7 OA and 17 control [CO]) were retrieved from a tissue bank. The MFC and MFT were imaged with μCT. Regions of interest (ROIs) were cranial (MFCcr; MTPcr) and caudal (MFCca; MTPca) sites. In each ROI, μCT images were scored for HAC fibrillation, surface mineralisation and for the presence of high-density mineralised protrusions (HDMP). The lesions were mapped, and site-matched histology was performed. The microstructure of healthy and abnormal HAC was discernible on μCT images and confirmed with histology. HAC fibrillation was more prevalent (p = 0.019) in the MFCcr of the OA group (n = 7/7, 100%) when compared with the CO group (n = 7/17, 41%). Score 1 HAC surface mineralisation was more prevalent (p = 0.038) in the OA MFCca (n = 4/7, 57%) when compared with the CO group (n = 2/17, 12%). HDMP were heterogenous and hyperdense mineralised material protruding into the HAC and were more frequent (p = 0.033) in MFCs (n = 12/24, 50%) compared with MTPs (n = 5/24, 20%). Score 3 HDMPs were also more prevalent (p = 0.003) in the MFCcr (n = 7/24, 29%) compared with MFCca (n = 0/24, 0%) and in MFCs (n = 7/24, 29%) compared with MTPs (n = 3/24, 12.5%) (p = 0.046). Clinical history was not available for all specimens. Equine HDMP and HAC surface mineralisation are imaged for the first time in the MFT joint. HAC fibrillation and erosion and HDMP are more frequent in the cranial aspect of the MFC. μCT images of OA in equine stifle joints provide a novel perspective of lesions and improve understanding of OA.

Comprehensive Study on Scoring and Grading Systems for Predicting the Severity of Knee Osteoarthritis.

Knee Osteoarthritis (KOA) is a degenerative joint ailment characterized by cartilage loss, which can be seen using imaging modalities and converted into imaging features. The older population is the most affected by knee OA, which affects 16% of people worldwide who are 15 years of age and older. Due to cartilage tissue degradation, primary knee OA develops in older people. In contrast, joint overuse or trauma in younger people can cause secondary knee OA. Early identification of knee OA, according to research, may be a successful management tactic for the condition. Scoring scales and grading systems are important tools for the management of knee osteoarthritis as they allow clinicians to measure the progression of the disease's severity and provide suggestions on suitable treatment at identified stages. The comprehensive study reviews various subjective and objective knee evaluation scoring systems that effectively score and grade the KOA based on where defects or changes in articular cartilage occur. Recent studies reveal that AI-based approaches, such as that of DenseNet, integrating the concept of deep learning for scoring and grading the KOA, outperform various state-of-the-art methods in order to predict the KOA at an early stage.

Therapeutic mechanisms of modified Jiawei Juanbi decoction in early knee osteoarthritis: A multimodal analysis

Modified Jiawei Juanbi decoction (MJD) is used for the treatment of early-stage knee osteoarthritis (KOA). Here, modified Jiawei Juanbi decoction (MJD) was employed for the treatment of early-stage knee osteoarthritis (KOA) and its mechanisms were assessed via metabonomics and network pharmacology. A total of 24 male Sprague-Dawley rats were randomly allocated into a normal control group, a model group, and an MJD group (n = 8 rats per group). Each rat group was further equally divided into two subgroups for investigation for either 14 or 28 days. A rat model of early-stage KOA was constructed and rats were treated with MJD. Effects were evaluated based on changes in knee circumference, mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). We also analyzed histopathological changes in articular cartilage. High-resolution mass spectrometry was used to analyze the chemical profile of MJD, identifying 228 components. Using an LC-Q-TOF-MS metabonomics approach, 33 differential metabolites were identified. The relevant pathways significantly associated with MJD include arginine and proline metabolism, vitamin B6 metabolism, as well as the biosynthesis of phenylalanine, tyrosine and tryptophan. The system pharmacology paradigm revealed that MJD contains 1027 components and associates with 1637 genes, of which 862 disease genes are related to osteoarthritis. The construction of the MJD composition-target-KOA network revealed a total of 140 intersection genes. A total of 39 hub genes were identified via integration of betweenness centrality values greater than 100 using CytoHubba. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed several significantly affected signaling pathways including the HIF-1, AGE-RAGE (in diabetic complications), IL-17, rheumatoid arthritis and TNF pathways. Integrated-omics and network pharmacology approaches revealed a necessity for further detailed investigation focusing on two major targets, namely NOS2 and NOS3, along with their essential metabolite (arginine) and associated pathways (HIF-1 signaling and arginine and proline metabolism). Real-time PCR validated significantly greater downregulation of NOS2 and HIF-1ɑ in the MJD as compared to the model group. Molecular docking analysis further confirmed the binding of active MJD with key active components. Our findings elucidate the impact of MJD on relevant pathophysiological and metabolic networks relevant to KOA and assess the drug efficacy of MJD and its underlying mechanisms of action.

Articular cartilage changes in patients with symptomatic rotator cuff tears: A prospective study with a mean 5-year follow-up

Articular cartilage changes in patients with symptomatic rotator cuff tears: A prospective study with a mean 5-year follow-up

OSTF1 knockdown mitigates IL-1β-induced chondrocyte injury via inhibiting the NF-κB signaling pathway

Osteoarthritis (OA) is an age-related joint disease characterized by progressive heterogeneous changes in articular cartilage and subchondral bone. Osteoclast stimulating factor 1 (OSTF1) is a small intracellular protein involved in bone formation and bone resorption. However, to our best knowledge, its role in OA is still unclear. In this study, an OA rat model was established by anterior cruciate ligament transection (ALCT). OSTF1 was increased in the cartilage tissues of OA patients and OA rats. Next, the role of OSTF1 in interleukin-1β (IL-1β)-induced chondrocyte apoptosis, inflammation and extracellular matrix degradation was explored through loss of function assays. Strikingly, OSTF1 knockdown relieved IL-1β-induced chondrocyte apoptosis, with decreased cleaved caspase-3 and cleaved PARP levels. Besides, OSTF1 knockdown restrained IL-1β-induced inflammation and degradation of extracellular matrix of chondrocytes. Subsequently, the molecular mechanism of OSTF1 was explored. Transcriptomic analysis revealed the potential gene network map regulated by OSTF1 knockdown. Some differentially expressed genes (DEGs) were involved in regulating the NF-κB signaling pathway. Furthermore, our results demonstrated that OSTF1 knockdown inhibited IL-1β-activated the NF-κB signaling pathway. Ultimately, we analyzed the potential gene network map regulated by OSTF1 and its downstream NF-κB. Bioinformatics analysis showed that 18 DEGs in OSTF1-silenced chondrocytes overlapped with the NF-κB downstream targets. Collectively, our findings indicate that OSTF1 knockdown mitigates IL-1β-induced chondrocyte injury via inhibiting the NF-κB signaling pathway.

Intra-articular injection of miRNA-1 agomir, a novel chemically modified miRNA agonists alleviates osteoarthritis (OA) progression by downregulating Indian hedgehog in rats

Our objective in this study is to determine whether intra-articular injection of miRNA-1 can attenuate the progression of OA in rats by down regulating Ihh. Knee chondrocytes were isolated from male Sprague–Dawley rats aged 2–3 days. Second-generation chondrocytes were transfected with miR-1 mimic and empty vector with lipo3000 for 6 h and then stimulated with 10 ng/mL IL-1β for 24 h. OA-related and cartilage matrix genes were quantified using real-time quantitative polymerase chain reaction (RT-qPCR). Two-month-old male Sprague–Dawley rats were divided into three groups (n = 30?): sham operation group + 50 µL saline, anterior cruciate ligament transection (ACLT) group + 50 µL miR-1 agomir (concentration), and control group ACLT + 50 µL miR-1 agomir. Treatment was started one week after the operation. All animals were euthanized eight weeks after the operation. X-rays and micro-CT were used to detect imaging changes in the knee joints. FMT was used to monitor joint inflammation in vivo. Safranin O staining was used to detect morphological changes in articular cartilage. Immunohistochemistry was used to detect Col2, Col10, metalloproteinase-13 (MMP-13). RT-qPCR was used to detect gene changes includingmiR-1, Col2, Col10, MMP-13, Ihh, Smo, Gli1, Gli2, and Gli3. Overexpression of miR-1 in IL-1β-stimulated chondrocytes reduced the levels of Ihh, MMP-13, and Col10 but increased the levels of Col2 and aggrecan. Intra-articular injection of miR-1 agomir reduced osteophyte formation, inflammation, and prevented cartilage damage. RT-qPCR results indicated that the miR-1 agomir increased articular cartilage anabolism and inhibited cartilage catabonism. miR-1 can attenuate the progression of OA by downregulating Ihh.

High-resolution magnetic resonance imaging can predict osteoarthritic progression after medial meniscus posterior root injury: randomized in vivo experimental study in a rabbit model

ImportanceThe field of meniscal root preservation has undergone significant advancement over the past decades; however, the challenge remains to fully understand whether meniscal root repair can ultimately arrest or delay osteoarthritic changes. ObjectiveTo assess longitudinal changes in articular cartilage, subchondral bone, and progression to meniscal extrusion (ME) using high-resolution magnetic resonance imaging (MRI). MethodsMedial meniscus posterior root tear was surgically induced in 39 New Zealand white rabbits. Animals were randomly assigned into three experimental groups: partial meniscectomy after root tear (PM, n ​= ​13); root tear left in situ (CT, n ​= ​13); and transtibial root repair (RR, n ​= ​13). Contralateral limbs were used as healthy controls. High resolution 4.7 Tesla MRI of the knee joint was performed at baseline, after 2-, and 4-months of post-surgery. Cartilage thickness was calculated in medial and lateral compartments. In addition, the evaluation of ME, subchondral bone edema and healing potential after root repair were assessed too. ResultsProgressive cartilage thinning, ME, and subchondral bone edema were evident in all 3 study groups after 4-months of follow-up. The mean cartilage thickness in the PM group was 0.53 ​mm (±0.050), 0.57 ​mm (±0.05) in the CT group, and 0.60 ​mm (±0.08) in the RR group. The PM group exhibited significantly higher cartilage loss when compared to the CT and RR groups (p ​< ​0.001). Moreover, progressive ME and subchondral bone edema were associated with a more severe cartilage loss at the final follow-up. ConclusionMeniscal root repair did not halt but rather reduced the progression of osteoarthritis (OA). Degenerative changes worsened at a rapid rate in the PM group compared to the RR and CT groups. Early cartilage swelling, persistent subchondral edema, and progressive ME predicted a more severe progression to knee OA in the CT and RR groups. Level of evidenceII.

Effects of intra-articular injection of platelet-rich plasma on the inflammatory process and histopathological characteristics of cartilage and synovium in animals with osteoarthritis: a systematic review with meta-analysis

BackgroundOsteoarthritis (OA) affects the entire joint, causing structural changes in articular cartilage, subchondral bone, ligaments, capsule, synovial membrane, and periarticular muscles that afflicts millions of people globally, leading to persistent pain and diminished quality of life. The intra-articular use of platelet-rich plasma (PRP) is gaining recognition as a secure therapeutic approach due to its potential regenerative capabilities. However, there is controversial clinical data regarding efficacy of PRP for OA treatment. In this context, gathering scientific evidence on the effects of PRP in treating OA in animal models could provide valuable insights into understanding its impact on aspects like cartilage health, synovial tissue integrity, and the inflammatory process in affected joints. Thus, the objective of this study was to assess the effects of PRP injections on inflammation and histopathological aspects of cartilage and synovium in animal models of OA through a comprehensive systematic review with meta-analysis.MethodsA electronic search was conducted on Medline, Embase, Web of Science, The Cochrane Library, LILACS, and SciELO databases for relevant articles published until June 2022. A random-effects meta-analysis was employed to synthesize evidence on the histological characteristics of cartilage and synovium, as well as the inflammatory process. The GRADE approach was utilized to categorize the quality of evidence, and methodological quality was assessed using SYRCLE’s RoB tool.ResultsTwenty-one studies were included in the review, with twelve of them incorporated into the meta-analysis. PRP treatment demonstrated superior outcomes compared to the control group in terms of cartilage histology (very low quality; p = 0.0002), synovium histology (very low quality; p < 0.0001), and reductions in proinflammatory markers, including IL-1 (low quality; p = 0.002), IL-6 (very low quality; p < 0.00001), and TNF-α (very low; p < 0.00001). However, PRP treatment did not yield a significant impact on PDGF-A levels (very low quality; p = 0.81).ConclusionPRP appears capable of reducing proinflammatory markers (IL-1, IL-6, TNF-α) and mitigating cartilage and synovium damage in animals with OA. However, the levels of evidence of these findings are low to very low. Therefore, more rigorous studies with larger samples are needed to improve the quality of evidence.PROSPERO registrationCRD42022250314

Phytochemicals against Osteoarthritis by Inhibiting Apoptosis.

Osteoarthritis (OA) is a chronic joint disease that causes pathological changes in articular cartilage, synovial membrane, or subchondral bone. Conventional treatments for OA include surgical and non-surgical methods. Surgical treatment is suitable for patients in the terminal stage of OA. It is often the last choice because of the associated risks and high cost. Medication of OA mainly includes non-steroidal anti-inflammatory drugs, analgesics, hyaluronic acid, and cortico-steroid anti-inflammatory drugs. However, these drugs often have severe side effects and cannot meet the needs of patients. Therefore, safe and clinically appropriate long-term treatments for OA are urgently needed. Apoptosis is programmed cell death, which is a kind of physiologic cell suicide determined by heredity and conserved by evolution. Inhibition of apoptosis-related pathways has been found to prevent and treat a variety of diseases. Excessive apoptosis can destroy cartilage homeostasis and aggravate the pathological process of OA. Therefore, inhibition of apoptosis-related factors or signaling pathways has become an effective means to treat OA. Phytochemicals are active ingredients from plants, and it has been found that phytochemicals can play an important role in the prevention and treatment of OA by inhibiting apoptosis. We summarize preclinical and clinical studies of phytochemicals for the treatment of OA by inhibiting apoptosis. The results show that phytochemicals can treat OA by targeting apoptosis-related pathways. On the basis of improving some phytochemicals with low bioavailability, poor water solubility, and high toxicity by nanotechnology-based drug delivery systems, and at the same time undergoing strict clinical and pharmacological tests, phytochemicals can be used as a potential therapeutic drug for OA and may be applied in clinical settings.

Effects of alendronate on cartilage lesions and micro-architecture deterioration of subchondral bone in patellofemoral osteoarthritic ovariectomized rats with patella-baja

BackgroundPatellofemoral osteoarthritis (PFJOA) is a subtype of knee OA, which is one of the main causes of anterior knee pain. The current study found an increased prevalence of OA in postmenopausal women, called postmenopausal OA. Therefore, we designed the ovariectomized rat model of patella baja-induced PFJOA. Alendronate (ALN) inhibits osteoclast-mediated bone loss, and has been reported the favorable result of a potential intervention option of OA treatment. However, the potential effects of ALN treatment on PFJOA in the ovariectomized rat model are unknown and need further investigation prior to exploration in the clinical research setting. In this study, the effects of ALN on articular cartilage degradation and subchondral bone microstructure were assessed in the ovariectomized PFJOA rat model for 10 weeks.MethodsPatella baja and estrogen withdrawal were induced by patellar ligament shortening (PLS) and bilateral ovariectmomy surgeries in 3-month-old female Sprague–Dawley rats, respectively. Rats were randomly divided into five groups (n = 8): Sham + V; OVX + V, Sham + PLS + V, OVX + PLS + V, OVX + PLS + ALN (ALN: 70 μg/kg/week). Radiography was performed to evaluate patellar height ratios, and the progression of PFJOA was assessed by macroscopic and microscopic analyses, immunohistochemistry and micro-computed tomography (micro-CT).ResultsOur results found that the patella baja model prepared by PLS can successfully cause degeneration of articular cartilage and subchondral bone, resulting in changes of PFJOA. OVX caused a decrease in estrogen levels in rats, which aggravated the joint degeneration caused by PFJOA. Early application of ALN can delay the degenerative changes of articular cartilage and subchondral bone microstructure in castrated PFJOA rat to a certain extent, improve and maintain the micrometabolism and structural changes of cartilage and subchondral bone.ConclusionThe early application of ALN can delay the destruction of articular cartilage and subchondral bone microstructure in castrated PFJOA rat to a certain extent.

Serial injections of 4% polyacrylamide hydrogel have no detrimental effects in equine joints following clinical, histologic, and synovial biomarker evaluation.

Polyacrylamide hydrogel (4% PAHG) is an inert viscoelastic supplement used to manage osteoarthritis in horses. Even with a prolonged clinical effect, horses may be administered multiple doses during their performance career. The effect of the serial 4% PAHG treatments is not known. The objectives of this study were to evaluate the clinical, histologic, and synovial fluid biomarker effects following serial administration of 4% PAHG in normal equine fetlock joints. 8 healthy horses. In a blinded, controlled in vivo study, horses received serial intra-articular injections of 4% PAHG (Noltrex Vet; Nucleus ProVets LLC) and contralateral 0.9% saline control on days 0, 45, 90, and 135. Treatment and control joints were randomly assigned. Synovial fluid was collected before administration of 4% PAHG or 0.9% saline on day 0 and at study completion for cellular and biomarker evaluation. Serial physical and lameness examinations were performed throughout the study. On day 240, gross examination and harvest of cartilage and synovial membrane for histology were completed. There were no histologic changes in articular cartilage or synovial fluid biomarkers. The 4% PAHG was seen on the surface of the synovium in 5 of 8 treated joints 105 days after the last treatment. There are minimal effects following serial injections of 4% PAHG on normal joints in horses following administration at 0, 45, 90, and 135 days, with final evaluation on day 240. Serial administration of intra-articular 4% PAHG in horses may provide long-term joint lubrication with no detrimental effects.

Inhibition of Phlpp1 preserves the mechanical integrity of articular cartilage in a murine model of post-traumatic osteoarthritis

ObjectivePhlpp1 inhibition is a potential therapeutic strategy for cartilage regeneration and prevention of post-traumatic osteoarthritis (PTOA). To understand how Phlpp1 loss affects cartilage structure, cartilage elastic modulus was measured with atomic force microscopy (AFM) in male and female mice after injury. MethodsOsteoarthritis was induced in male and female Wildtype (WT) and Phlpp1-/- mice by destabilization of the medial meniscus (DMM). At various timepoints post-injury, activity was measured, and knee joints examined with AFM and histology. In another cohort of WT mice, the PHLPP inhibitor NSC117079 was intraarticularly injected four weeks after injury. ResultsMale WT mice showed decreased activity and histological signs of cartilage damage at 12 but not 6 weeks post-DMM. Female mice showed a less severe response to DMM by comparison, with no histological changes seen at any timepoint. In both sexes the elastic modulus of medial condylar cartilage was decreased in WT mice but not Phlpp1-/- mice after DMM as measured by AFM. By 6 weeks, cartilage modulus had decreased from 2MPa to 1MPa in WT mice. Phlpp1-/- mice showed no change in modulus at 6 weeks and only a 25% decrease at 12 weeks. The PHLPP inhibitor NSC117079 protected cartilage structure and prevented signs of OA 6 weeks post-injury. ConclusionsAFM is a sensitive method for detecting early changes in articular cartilage post-injury. Phlpp1 suppression, either through genetic deletion or pharmacological inhibition, protects cartilage degradation in a model of PTOA, validating Phlpp1 as a therapeutic target for PTOA.

Quantitative Magnetic Resonance Imaging of Lateral Compartment Articular Cartilage After Lateral Extra-articular Tenodesis

Background: Concerns have arisen that anterior cruciate ligament reconstruction (ACLR) with lateral extra-articular tenodesis (LET) may accelerate the development of posttraumatic osteoarthritis in the lateral compartment of the knee. Purpose/Hypothesis: The purpose of this study was to evaluate whether the augmentation of ACLR with LET affects the quality of lateral compartment articular cartilage on magnetic resonance imaging (MRI) at 2 years postoperatively. We hypothesized that there would be no difference in T1rho and T2 relaxation times when comparing ACLR alone with ACLR + LET. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A consecutive subgroup of patients at the Fowler Kennedy Sport Medicine Clinic participating in the STABILITY 1 Study underwent bilateral 3-T MRI at 2 years after surgery. The primary outcome was T1rho and T2 relaxation times. Articular cartilage in the lateral compartment was manually segmented into 3 regions of the tibia (lateral tibia [LT]–1 to LT-3) and 5 regions of the femur (lateral femoral condyle [LFC]–1 to LFC-5). Analysis of covariance was used to compare relaxation times between groups, adjusted for lateral meniscal tears and treatment, cartilage and bone marrow lesions, contralateral relaxation times, and time since surgery. Semiquantitative MRI scores according to the Anterior Cruciate Ligament OsteoArthritis Score were compared between groups. Correlations were used to determine the association between secondary outcomes (including results of the International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score, Lower Extremity Functional Scale, 4-Item Pain Intensity Measure, hop tests, and isokinetic quadriceps and hamstring strength tests) and cartilage relaxation. Results: A total of 95 participants (44 ACLR alone, 51 ACLR + LET) with a mean age of 18.8 years (61.1% female [58/95]) underwent 2-year MRI (range, 20-36 months). T1rho relaxation times were significantly elevated for the ACLR + LET group in LT-1 (37.3 ± 0.7 ms vs 34.1 ± 0.8 ms, respectively; P = .005) and LFC-2 (43.9 ± 0.9 ms vs 40.2 ± 1.0 ms, respectively; P = .008) compared with the ACLR alone group. T2 relaxation times were significantly elevated for the ACLR + LET group in LFC-1 (51.2 ± 0.7 ms vs 49.1 ± 0.7 ms, respectively; P = .03) and LFC-4 (45.9 ± 0.5 ms vs 44.2 ± 0.6 ms, respectively; P = .04) compared with the ACLR alone group. All effect sizes were small to medium. There was no difference in Anterior Cruciate Ligament OsteoArthritis Scores between groups (P = .99). Weak negative associations (rs = –0.27 to –0.22; P < .05) were found between relaxation times and quadriceps and hamstring strength in the anterolateral knee, while all other correlations were nonsignificant (P > .05). Conclusion: Increased relaxation times demonstrating small to medium effect sizes suggested early biochemical changes in articular cartilage of the anterolateral compartment in the ACLR + LET group compared with the ACLR alone group. Further evidence and long-term follow-up are needed to better understand the association between these results and the potential risk of the development of osteoarthritis in our patient cohort.

MRI-based cartilage changes and clinical effectiveness of autologous intra-articular platelet-rich plasma injections in symptomatic patients with moderate osteoarthritis of the knee

BackgroundAn autologous blood product containing a high percentage of various growth factors, cytokines, and modulating factors such as platelet-rich plasma (PRP) is thought to play a role in chondral remodeling by promoting the production of cartilage matrix molecules and repairing and regenerating articular cartilage. In symptomatic patients with moderate osteoarthritis (OA) of the knee, we aimed to investigate MRI-based cartilage changes and the clinical efficacy of autologous intra-articular PRP injections.ResultsThirty-three patients with grades 2 and 3 OA of knees as per Kellgren and Lawrence OA classification underwent three consecutive PRP injections at monthly intervals. These patients were followed up monthly for the first 3 months, and then after every 3 months at 6 months, 9 months, and 12 months. There was statistically significant improvement in joint pain and functionality with the visual analogue scale (VAS) scores showing a reduction from 7 ± 2 at baseline to 2.76 ± 1.34 at 12 months and Western Ontario and McMaster Universities Osteoarthritis Index Score (WOMAC) scores declining from 77.91 ± 1 1.6 at baseline to 23.61 ± 19.1 at 12 months (p < 0.05). The reduction in VAS and WOMAC scores was maximum during the first 3 months after PRP therapy. MRI showed a statistically insignificant improvement in cartilage thickness [Whole Organ Magnetic Resonance Imaging Score (WORMS) 3.15 ± 1.41 to 3.3 ± 0.84) (p > 0.05)].ConclusionsPRP had a positive effect on pain alleviation and patient functioning, but there was no significant change in articular cartilage as measured by MRI.