Joint Damage In Osteoarthritis Research Articles

Targeting Synovial Lymphatic Function as a Novel Therapeutic Intervention for Age-Related Osteoarthritis in Mice.

The synovial lymphatic system (SLS) removes catabolic factors from the joint. Vascular endothelial growth factor C (VEGF-C) and its receptor, VEGFR-3, are crucial for lymphangiogenesis. However, their involvement in age-related osteoarthritis (OA) is unknown. This study was undertaken to determine whether the SLS and the VEGF-C/VEGFR-3 pathway contribute to the development and progression of age-related OA, using a murine model of naturally occurring joint disease. SLS function was assessed in the knees of young (3-month-old) and aged (19-24-month-old) male and female C57BL/6J mice via a newly established in vivo IVIS-dextran imaging approach, which, in addition to histology, was used to assess the effects of VEGF-C treatment on SLS function and OA pathology in aged mice. RNA-sequencing of synovial tissue was performed to explore molecular mechanisms of the disease in the mouse knee joints. Results showed that aged mice had impaired SLS function, including decreases in joint clearance (mean T1/2 of signal intensity clearance, 2.8 hours in aged mice versus 0.5 hours in young mice; P < 0.0001), synovial influx (mean ± SD 1.7 ± 0.8% in aged mice versus 4.1 ± 1.9% in young mice; P=0.0004), and lymph node draining capacity (mean ± SD epifluorescence total radiant intensity ([photons/second]/[μW/cm2 ]) 1.4 ± 0.8 in aged mice versus 3.7 ± 1.2 in young mice; P < 0.0001). RNA-sequencing of the synovial tissue showed that Vegf-c and Vegfr3 signaling genes were decreased in the synovium of aged mice. VEGF-C treatment resulted in improvements in SLS function in aged mice, including increased percentage of signal intensity joint clearance (mean ± SD 63 ± 9% in VEGF-C-treated aged mice versus 52 ± 15% in vehicle-treated aged mice; P=0.012), increased total articular cartilage cross-sectional area (mean ± SD 0.38 ± 0.07 mm2 in VEGF-C-treated aged mice versus 0.26 ± 0.07 mm2 in vehicle-treated aged mice; P < 0.0001), and decreased percentage of matrix metallopeptidase 13-positive staining area within total synovial area in 22-month-old VEGF-C-treated mice versus 22-month-old vehicle-treated mice (mean ± SD decrease 7 ± 2% versus 4 ± 1%; P=0.0004). SLS function is reduced in the knee joints of aged mice due to decreased VEGF-C/VEGFR-3 signaling. VEGF-C treatment attenuates OA joint damage and improves synovial lymphatic drainage in aged mice. The SLS and VEGF-C/VEGFR-3 signaling represent novel physiopathologic mechanisms that could potentially be used as therapeutic targets for age-related OA.

The Effect of Alcoholic Essence Satureja Sahandica Bornm L. on the Expression of Metalloproteinases 1, 2, 9 and 13 in a Model Similar to Osteoarthritis

Loss of the extracellular matrix of cartilage is one of the most important and prominent features of osteoarthritis (OA). The ECM has two important components, including the proteoglycan aggrecan and type II collagen, which are the main targets of MMPs and ADAM TSs enzymes. In this paper, the effect of ASSB Compared with dexamethasone and ibuprofen as representatives of steroidal and nonsteroidal anti-inflammatory drugs. One way to prevent irreversible joint damage in OA is to inhibit MMPs. ASSB can improve the condition of patients with osteoarthritis by reducing the expression of the MMPs 9 and 13 gene. <i>Background</i>: OA is a progressive joint disease characterized by cartilage degeneration, cartilage bone regeneration, and synovial membrane inflammation and is exacerbated with age. Given the side effects of conventional OA treatments, including nonsteroidal anti-inflammatory drugs and corticosteroids, it is important to consider new treatments for this disorder. Recently, the effect of matrix metalloproteinases on the pathogenesis of OA has been attracted attention. <i>Objective</i>: The aim of this paper was to evaluate the impact of Alcoholic Satureja Sahandica Bornem L. (ASSB) essence on inhibiting the expression of metalloproteinase gene 1, 2, 9 and 13 in bovine fibroblast-like synoviocytes stimulated by lipopolysaccharide as a model of osteoarthritis. <i>Methods</i>: Synovial cells were isolated from the articular cartilage of the radiocarpal joint of an 8-month-old Holstein cow. After determining the degree of toxicity by MTT Assay, the cells were exposed to stimulation of LPS without or in the presence of dexamethasone, ibuprofen and alcoholic Satureja Sahandica Bornem essence (ASSB). Metalloproteinase gene expression 1, 2, 9 and 13 were measured by RT-PCR and ELISA. The effect of ASSB on migration and cell invasion was investigated by Transwell chambers. <i>Results</i>: The results showed that Satureja Sahandica Bornm (SSB) essential oil significantly reduced the expression of metalloproteinases 9 and 12 in bovine fibroblast-like synovocytes stimulated by lipopolysaccharide. It also suppressed migration and invasion of these cells. However, Satureja Sahandica Bornm L. had no significant impact on the expression of MMPs 1 and 2. <i>Conclusion</i>: Based on our results, ASSB can significantly reduce the activity and inflammatory effect of MMPs 9 and 12 in OA, its potential role as a complement to NSAIDs and common corticosteroids was confirmed. However, cellular modeling does not confirm the beneficial effect of OA in patients.

Chaperone-mediated autophagy is a hallmark of joint damage in osteoarthritis

Purpose: In osteoarthritis (OA), defects in Autophagy mechanisms are evident and precede joint damage. Therefore, identifying biomarkers associated with autophagy defects could facilitate the development of personalized therapeutic strategies to prevent OA progression.

Biomarkers of Joint Damage in Osteoarthritis: Current Status and Future Directions.

Osteoarthritis (OA) is a disease of the whole joint organ, characterized by the loss of cartilage, and structural changes in bone including the formation of osteophytes, causing disability and loss of function. It is also associated with systemic mediators and low-grade inflammation. Currently, there is negligible/no availability of specific biomarkers that can be used to facilitate the diagnosis and treatment of OA. The most unmet clinical need is, however, related to the monitoring of disease progression over a short period that can be used in clinical trials. In this review, the value of biomarkers identified over the past decade has been highlighted. These biomarkers are associated with the synthesis and breakdown of cartilage, including collagenous and noncollagenous biomarkers, inflammatory and anti-inflammatory biomarkers, expressed in the biological fluid such as serum, synovial fluid, and urine. Broad validation of novel and clinically applicable biomarkers and their involvement in the pathways are particularly needed for early-stage diagnosis, monitoring disease progression, and severity and examining new drugs to mitigate the effects of this highly prevalent and debilitating condition.

Neuroimmune interactions and osteoarthritis pain: focus on macrophages.

Bidirectional interactions between the immune system and the nervous system are increasingly appreciated as playing a pathogenic role in chronic pain. Unraveling the mechanisms by which inflammatory pain is mediated through communication between nerves and immune cells may lead to exciting new strategies for therapeutic intervention. In this narrative review, we focus on the role of macrophages in the pathogenesis of osteoarthritis (OA) pain. From regulating homeostasis to conducting phagocytosis, and from inducing inflammation to resolving it, macrophages are plastic cells that are highly adaptable to their environment. They rely on communicating with the environment through cytokines, growth factors, neuropeptides, and other signals to respond to inflammation or injury. The contribution of macrophages to OA joint damage has garnered much attention in recent years. Here, we discuss how macrophages may participate in the initiation and maintenance of pain in OA. We aim to summarize what is currently known about macrophages in OA pain and identify important gaps in the field to fuel future investigations.

OATargets: a knowledge base of genes associated with osteoarthritis joint damage in animals

ObjectivesTo collate the genes experimentally modulated in animal models of osteoarthritis (OA) and compare these data with OA transcriptomics data to identify potential therapeutic targets.MethodsPubMed searches were conducted to identify...

Dietary Saturated Fatty Acids Modulate Pain Behaviour in Trauma-Induced Osteoarthritis in Rats.

Osteoarthritis (OA) is a degenerative condition of joints, causing pain and swelling, and can be caused or worsened by trauma and obesity. The objectives of this study were to determine whether pain behaviour and progression of OA were increased in rats with trauma-induced OA fed dietary saturated fatty acids (SFA). Male Wistar rats were fed either a corn starch diet (C) or high-carbohydrate high-fat diet (H) with either 20% beef tallow or SFA (lauric (HLA), myristic (HMA), palmitic (HPA) or stearic (HSA) acids) for 16 weeks prior to and 8 weeks after excision of the medial meniscus of right knee joint to initiate OA when pain behaviour, glial activity, progression of knee OA, inflammatory mediators and signs of metabolic syndrome were assessed. Rats fed beef tallow, palmitic or stearic acids showed increased pain symptoms characterised by decreased hind paw/limb withdrawal thresholds and grip strengths and increased spinal astrogliosis and microgliosis compared to rats fed lauric or myristic acids. However, the severity of OA joint damage was unchanged by these dietary manipulations. We conclude that pain symptoms of trauma-induced OA in rats worsen with increased dietary beef tallow or palmitic or stearic acids, but improve with lauric or myristic acids, despite unchanged OA cartilage damage.

Berberine-mediated up-regulation of surfactant protein D facilitates cartilage repair by modulating immune responses via the inhibition of TLR4/NF-ĸB signaling

The innate immune system drives inflammatory joint damage in osteoarthritis (OA) and regulates cartilage repair. Berberine chloride (BBR) is an isoquinoline alkaloid that shows immunomodulatory activity in a variety of cell lines. However, the immunomodulatory mechanisms of BBR in chondrocytes during OA are largely unknown. Herein, we assessed the ability of BBR to mediate chondroprotection through its effects on innate immunity. We found that BBR up-regulated the expression of surfactant protein D (SP-D) in OA cartilage, a key regulator of inflammation and innate immunity both in the airways and extrapulmonary tissues, including joint cartilage. To further explore these findings, we used recombinant adeno-associated virus (rAAV)-mediated knockdown of SP-D. Silencing was assessed in rat model of surgically-induced OA in the presence or absence of BBR treatment, 10 weeks post-surgery. We observed a clear improvement in histological scores of BBR-treated animals compared to those treated with BBR and the rAAV-SP-D vector. In addition, animals co-treated with BBR + recombinant human SP-D (rhSP-D) exhibited significantly lower histological scores than those treated with BBR alone. BBR treatment led to significantly reduced immune cell infiltration mediated through TLR4, F4/80, CD68 and CD34, whilst SP-D silencing reversed this improvement. In contrast, rhSP-D treatment enhanced the protective phenotype. We further explored how BBR influences SP-D and other OA-associated genes in vitro. We observed an up-regulation of SP-D and a marked decline in TRAF6, TLR4, MD-2 and MyD88 expression, as well as NF-κB p65 and IκBα phosphorylation in chondrocytes treated with sodium nitroprusside. siRNAs specific for SP-D were able to partially reverse this phenotype, whilst both rhSP-D and the TLR4 inhibitor TAK-242 enhanced the effects. Together, these results are consistent with a model wherein SP-D has therapeutic potential for OA treatment. Concomitantly, BBR modulates immune responses and decreases cartilage degradation. These findings suggest that BBR achieves this function through releasing SP-D from MD2/SP-D complexes and through the inhibition of TLR4/NF-κB signaling.

Nociceptive neuroplasticity of the murine knee joint precedes severe structural joint damage in a surgical model of OA

Purpose: Surgical destabilization of the medial meniscus (DMM) in the mouse knee results in slowly progressive osteoarthritis (OA), characterized by mild-to-moderate joint damage by week 8 and severe damage by week 16 after surgery. Progressive joint damage is associated with pain-related behaviors. Using NaV1.8-tdTomato reporter mice, which express a bright red fluorescent tdTomato reporter in >90% of C-nociceptors (pain-sensing neurons), we recently reported that DMM surgery led to changes in the anatomical distribution of nociceptors in the medial compartment of the knee. Specifically, in association with severe structural joint damage 16 weeks after DMM, the medial compartment of OA knees showed increased NaV1.8+ innervation in the medial synovium and meniscus, and NaV1.8+ nociceptors in subchondral bone channels. Here, we analyzed the nociceptive innervation of the knee in the early stages of experimental OA, 4 and 8 weeks after DMM. Methods: DMM or sham surgery was performed in the right knee of 10-week old male C57BL/6 NaV1.8-tdTomato mice. Four and eight weeks after surgery, n=3 mice/group mice were perfused transcardially with paraformaldehyde, and the right knees collected, post fixed and decalcified. Twenty-μm thick coronal frozen sections were collected at mid-joint level, and imaged using a confocal microscope. NaV1.8-tdTomato signal of the medial synovium was quantified using ImageJ. Channels observed in the subchondral bone of the medial femoral condyles and tibial plateaux that contained NaV1.8+ nerves were quantified as follows: two mid-joint sections (80 μm apart) per knee were used to count NaV1.8+ channels; the counts were averaged for each knee. Results: As previously reported, 4 and 8 weeks after DMM surgery, cartilage damage in the femur and tibia was very mild and limited to slight loss of proteoglycans. In addition, DMM mice had maximal subchondral bone sclerosis in the medial compartment by week 4. Despite the limited cartilage damage at this stage, analysis of the NaV1.8+ signal showed striking changes in the nociceptive innervation after DMM surgery, compared to controls. Firstly, we detected an increase in NaV1.8 innervation of the medial synovium, as early as 4 weeks after DMM, and no further increase weeks 8-16 (Fig. 1). Secondly, NaV1.8+ nociceptors were observed in the subchondral bone pointing toward calcified cartilage, and this as early as week 4. Conclusions: These findings suggest that the NaV1.8 nociceptive innervation of the mouse knee changes very rapidly after DMM surgery, and this before the onset of significant joint damage. While the biological significance of this observation needs to be established, it suggests that neuroplasticity of sensory nerves is an early feature of OA joint damage, which may contribute to joint disease.

Effects of carrageenan induced synovitis on joint damage and pain in a rat model of knee osteoarthritis

Knee osteoarthritis (OA) is associated with ongoing pain and joint damage that can be punctuated by acute flares of pain and inflammation. Synovitis in normal knees might resolve without long-term detriment to joint function. We hypothesised that osteoarthritis is associated with impaired resilience to inflammatory flares. We induced synovitis by injecting carrageenan into rat knees with or without meniscal transection (MNX)-induced OA, and measured synovitis, weightbearing asymmetry (pain behaviour), and joint damage up to 35 days after OA induction (23 days after carrageenan-injection). Carrageenan injection induced weightbearing asymmetry for 1 week, transient increase in knee diameter for 2 days, and a sustained increase in synovial macrophages, endothelial cell proliferation and vascular density compared with naive vehicle-injected controls. MNX surgery induced weightbearing asymmetry and histological evidence of OA. Carrageenan-injection in MNX-operated knees was followed for 2 days by increased weightbearing asymmetry compared either to MNX+vehicle or to sham+carrageenan groups. OA structural damage and synovitis at day 35 were greater in MNX+carrageenan compared to MNX+vehicle and sham+carrageenan groups. Carrageenan injection did not induce OA in Sham-operated knees. Intra-articular injection of the pro-inflammatory compound carrageenan in OA and sham-operated control knees induced a short term increase in joint pain. Even though pain flares resolved in both groups and damage was not induced in sham-operated knees, carrageen injection exacerbated long-term joint damage in OA knees. OA knees display less resilience to inflammatory episodes. Preventing inflammatory flares may be particularly important in preventing symptoms and long term joint damage in OA.

Native joint-resident mesenchymal stem cells for cartilage repair in osteoarthritis.

The role of native (not culture-expanded) joint-resident mesenchymal stem cells (MSCs) in the repair of joint damage in osteoarthritis (OA) is poorly understood. MSCs differ from bone marrow-residing haematopoietic stem cells in that they are present in multiple niches in the joint, including subchondral bone, cartilage, synovial fluid, synovium and adipose tissue. Research in experimental models suggests that the migration of MSCs adjacent to the joint cavity is crucial for chonodrogenesis during embryogenesis, and also shows that synovium-derived MSCs might be the primary drivers of cartilage repair in adulthood. In this Review, the available data is synthesized to produce a proposed model in which joint-resident MSCs with access to superficial cartilage are key cells in adult cartilage repair and represent important targets for manipulation in 'chondrogenic' OA, especially in the context of biomechanical correction of joints in early disease. Growing evidence links the expression of CD271, a nerve growth factor (NGF) receptor by native bone marrow-resident MSCs to a wider role for neurotrophins in OA pathobiology, the implications of which require exploration since anti-NGF therapy might worsen OA. Recognizing that joint-resident MSCs are comparatively abundant in vivo and occupy multiple niches will enable the optimization of single-stage therapeutic interventions for OA.

Potential biomarkers of haemophilic arthropathy: correlations with compatible additive magnetic resonance imaging scores.

Although biomarkers are useful diagnostic tools to assess joint damage in osteoarthritis and rheumatoid arthritis, few data exist for biomarkers of haemophilic arthropathy. To evaluate the association between biomarkers and compatible additive magnetic resonance imaging (MRI) scores in patients with severe haemophilia A. Patients aged 12-35 years with no history of factor VIII (FVIII) inhibitors were enrolled in a controlled, cross-sectional, multinational investigation. Patients received primary or secondary prophylaxis or on-demand treatment with FVIII and underwent MRI on four joints (two ankles, two knees). Soluble biomarkers of cartilage and bone degradation, inflammation, and angiogenesis were assessed (serum levels of C-terminal telopeptides of type I collagen [CTX-I], cartilage oligomeric matrix protein [COMP], chondroitin-sulphate aggrecan turnover 846 epitope [CS846], tissue inhibitor of metalloproteinase 1 [TIMP-1]; plasma levels of vascular endothelial growth factor [VEGF], matrix metalloproteinases 3 and 9 [MMP3, MMP9]). Relationships between biomarkers and MRI scores were evaluated using Spearman rank correlation. Biomarkers were assessed in 117 of 118 per-protocol patients. Mean and median CTX-I, COMP, TIMP-1, MMP3, MMP9, and VEGF values were within normal ranges (reference range not available for CS846 in healthy volunteers). No correlations between biomarkers and MRI scores were found, with the exception of CS846, which showed significant correlation in a subgroup of 22 on-demand patients (r = 0.436; P = 0.04). Compatible additive MRI scores showed no clear correlations with any of the potential biomarkers for haemophilic arthropathy in the overall population. CS846 levels were significantly correlated with MRI scores in patients treated on demand.

Effects of ethanol extracts and compounds from Astragali radix on chondrocytes and MIA-induced osteoarthritis model in rat

This work was carried out to evaluate the effects of extract from the radix of Astragalus membranaceus (AR) and the natural product from AR on SW1353 Hyman chondrocytes and monosodium iodoacetate (MIA)-induced osteoarthritis (OA) model in rat. Ethanolic extract (ARE, 100, 200, 400 mg/kg) from AR were orally administered once a day for 14 days after the MIA injection. Administration of ARE to the MIA-induced OA rats decreased significantly knee arthritis scoring. The histopathological analyses showed remarkably that ARE treatment alleviated the severe joint damage such as the loss of necrotic chondrocytes and cartilage erosion in cartilage of MIA-OA model. ARE decreased significantly histopathological scoring to the level of 68.6 and 61.8% at the treatment of 200 and 400 mg/kg of ARE, respectively. ARE and butanol fraction from ARE inhibited the expression of matrix metalloproteinase-13 (MMP-13) mRNA in IL-1β-treated SW1353 cells. Eight compounds isolated from the ethyl acetate fraction of 80% methanol extract were tested for inhibitory effect on the production of MMPs in IL-1β-treated SW1353 cells. Isoastragaloside II revealed the inhibition of 21.3, 16.8 18.8, 8.2 and 23.5% on MMP-1, MMP-3, MMP-13, MMP-2 and MMP-9, respectively, at 10µM treatment, comparing to control. Calycosin exhibited the inhibition of 23.5, 39.8, 13.7, 15.9 and 23.4% on MMP-1, MMP-3, MMP-13, MMP-2 and MMP-9, respectively, at 40µM treatment, comparing to control. These results indicated that ARE might be useful in protecting and alleviating joint damage in OA through preventing chondrocyte injury and extracellular matrix degradation.

The protective effects of Donepezil (DP) against cartilage matrix destruction induced by TNF-α

The extracellular matrix apparatuses containing collagen and proteoglycan (aggrecan) are important factors for maintaining the integrity of cartilage. Collagen type II, the main component of total cartilage, is mainly degraded by matrix metalloproteinase13 (MMP-13), which is an important molecule responsible for joint damage in Osteoarthritis (OA). Donepezil (DP), a potent and selective acetylcholinesterase inhibitor, is a medication approved by the US Food and Drug Administration and used in the alleviation of dementia in Alzheimer’s disease (AD). In this study, we found that DP treatment prevented the degradation of collagen type II induced by TNF-α. Mechanistically, DP treatment leads to the inhibition of the transcriptional activity of interferon response factor-1 (IRF-1), thereby prevents the induction of MMP-13. These findings suggest the potential therapeutic effects of DP in OA.

Cilostazol prevents the degradation of collagen Type II in human chondrocytes

The alteration of extracellular matrix (ECM) in cartilage during the pathological development of Osteoarthritis (OA) changes the biomechanical environment of chondrocytes, which further drives the progression of the disease in the presence of inflammation. Healthy cartilage matrix mainly contains collagen type II, which is degraded by matrix metalloproteinase13 (MMP13), an important molecules responsible for joint damage in OA. Cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2-(1H)-quinolinone) is a medication approved by the US Food and Drug Administration and used in the alleviation of the symptom of intermittent claudication in individuals with peripheral vascular disease. In this study, we reported that cilostazol is able to suppress the degradation of type II collagen in human chondrocytes induced by IL-1β. Mechanistically, cilostazol treatment leads to inhibiting the expression of IRF-1, thereby prevents the induction of MMP-13. Signal transducers and activator of transcription 1 (STAT1) has been reported to play an essential role in regulating the activation of IRF-1. Our results indicated that cilostazol suppresses the activation of STAT1 by mitigating the phosphorylation of STAT1 at Ser727 and tyrosine phosphorylation of STAT1 at position 701 (Tyr701).

THU0455 Transcriptomics to Identify Synovial Genes and Pathways Associated with Disease Progression in A Cohort of Early Osteoarthritis Patients (CHECK)

BackgroundIf and how the synovial activation that is observed in over 50% of osteoarthritis (OA) patients contributes to irreversible joint pathology, is not known.ObjectivesTo identify pathways that may determine progression...

Effect of osteopontin on TIMP-1 and TIMP-2 mRNA in chondrocytes of human knee osteoarthritis in vitro.

Tissue inhibitors of metalloproteinases (TIMPs) regulate the activity of matrix metalloproteinases (MMPs) and enzymes from the a disintegrin and metalloproteinase domain with thrombospondin motifs family in osteoarthritis (OA). Elevated osteopontin (OPN) levels in plasma, synovial fluid and articular cartilage are associated with progressive OA joint damage; however, the role of OPN in the pathological changes of knee OA remains undetermined. The present study was undertaken to examine the effect of OPN on the expression of TIMP-1 and TIMP-2 mRNA in chondrocytes from 16 patients with knee OA. In this study, following the stimulation of human chondrocytes with recombinant human OPN (rhOPN; 100 ng/ml and 1 μg/ml, respectively) for 48 h, MTT assay was used to determine cell viability while the quantitative polymerase chain reaction (PCR) was used to detect the alterations in TIMP-1 and TIMP-2 levels. The results illustrated that neither 100 ng/ml nor 1 μg/ml rhOPN caused cytotoxicity or apoptosis of chondrocytes and that the relative mRNA expression of TIMP-1 and TIMP-2 was significantly increased in the 1 μg/ml rhOPN group compared with that in the control group (P=0.022 and P=0.003, respectively). However, no significant difference in expression was revealed between the 100 ng/ml rhOPN and control groups (P=0.998 and P=0.209, respectively). In conclusion, OPN may have a protective effect against pathological changes in advanced-stage OA.

Expression of CD44 in articular cartilage is associated with disease severity in knee osteoarthritis

Objectives To investigate CD44 levels in articular cartilage of knee osteoarthritis (OA) and the relationship between CD44 and severity of the disease.Methods All 50 cartilage tissues included normal and OA cartilage, and were ascribed to the following four groups on the basis of modified Mankin score: normal, mild lesions, moderate lesions and severe lesions. CD44 levels in articular cartilage were assessed by immunohistochemical methods.Results CD44 levels were detected in all four groups. The difference in average gray value of CD44 expression showed statistical significance when compared between each group (P < 0.05). In addition, CD44 expression in each group correlated with disease severity, according to the modified Mankin score (ρ = −0.848, P < 0.01).Conclusions CD44 in articular cartilage is associated with progressive knee OA joint damage.

Correlation between senescence-associated beta-galactosidase expression in articular cartilage and disease severity of patients with knee osteoarthritis.

The purposes of this study were to investigate senescence-associated beta-galactosidase (SA-beta-Gal) levels in articular cartilage of knee osteoarthritis (OA) and the relationship with severity of the disease. All the 50 cartilage tissues, including normal (controls) and OA cartilage were ascribed to four groups of normal, mild lesions, moderate lesions and severe lesions on the basis of the modified Mankin score. Immunohistochemistry was used to assess the SA-beta-Gal expression in articular cartilage. No SA-beta-Gal staining was observed in the normal articular cartilage samples. SA-beta-Gal staining was found in a subset of the chondrocytes close to the lesion site of mild, moderate and severe damaged knee OA cartilage. The percentage of SA-beta-Gal-positive chondrocytes in articular cartilage was 0% in controls, 13.00±5.77% in mild lesions, 31.65±6.91% in moderate lesions and 51.95±6.21% in severe lesions. SA-beta-Gal expression in mild lesions, moderate lesions and severe lesions was higher compared with that of controls (P<0.0001). SA-beta-Gal expression in moderate lesions and severe lesions were higher with respect to mild lesion samples (P<0.0001). SA-beta-Gal expression in severe lesions was elevated compared with those of moderate lesions (P<0.0001). Subsequent analysis showed that articular cartilage SA-beta-Gal levels correlated with severity of disease (Spearman's ρ=0.94, P<0.0001). SA-beta-Gal expression in articular cartilage is associated with progressive knee OA joint damage and is a potential indictor of disease severity.

Impaired muscle function in a mouse surgical model of osteoarthritis

Impaired muscle function in a mouse surgical model of osteoarthritis