Increase In Cartilage Thickness Research Articles

Effectiveness of Artocarpus altilis (Parkinson ex F.A.Zorn) Fosberg ethanol extract in suppressing inflammation and cartilage degeneration in animal models of osteoarthritis

Context: Osteoarthritis (OA) is a degenerative joint disease characterized by an inflammatory reaction and cartilage degradation. Artocarpus altilis is a well-known traditional medicine with various phenolic and flavonoid content. Several pharmacological properties of A. altilis extract (AAE) have been reported, but its effectiveness in osteoarthritis is unknown. Aims: To investigate the potential of AAE as an anti-osteoarthritis. Methods: The Wistar rats induced OA with mono-iodoacetate (MIA). The OA model rats were treated with AAE with three dose levels (100, 200, and 400 mg/kg) for 28 days. As a positive control used Na-diclofenac (20 mg/kg). Serum IL-1β, IL-10, MMP-3, and MMP-13 levels and histopathological profiles were compared to the MIA group and normal control (5% Na-CMC). Results: The experimental results showed that AAE could significantly suppress the production of inflammatory mediator factor IL-1β, matrix-degrading proteinase MMP-3, MMP-13, and cartilage degeneration. In addition, AAE increased the production of the anti-inflammatory mediator IL-10, improved synovial inflammation, and increased cartilage thickness. Conclusions: A. altilis extract has the potential to be developed as an anti-osteoarthritis therapeutic agent from natural medicine.

Lei's formula attenuates osteoarthritis mediated by suppression of chondrocyte senescence via the mTOR axis: in vitro and in vivo experiments.

Lei's formula (LSF), a traditional Chinese herbal remedy, is recognized for its remarkable clinical effectiveness in treating osteoarthritis (OA). Despite its therapeutic potential, the exact molecular mechanisms underlying LSF's action in OA have remained enigmatic. Existing research has shed light on the role of the mTOR signaling pathway in promoting chondrocyte senescence, a central factor in OA-related cartilage degeneration. Consequently, targeting mTOR to mitigate chondrocyte senescence presents a promising avenue for OA treatment. The primary objective of this study is to establish LSF's chondroprotective potential and confirm its anti-osteoarthritic efficacy through mTOR inhibition. In vivo assessments using an OA mouse model reveal substantial articular cartilage degeneration. However, LSF serves as an effective guardian of articular cartilage, evidenced by reduced subchondral osteosclerosis, increased cartilage thickness, improved surface smoothness, decreased OARSI scores, elevated expression of cartilage anabolic markers (Col2 and Aggrecan), reduced expression of catabolic markers (Adamts5 and MMP13), increased expression of the chondrocyte hypertrophy marker (Col10), and decreased expression of chondrocyte senescence markers (P16 and P21). In vitro findings demonstrate that LSF shields chondrocytes from H2O2-induced apoptosis, inhibits senescence, enhances chondrocyte differentiation, promotes the synthesis of type II collagen and proteoglycans, and reduces cartilage degradation. Mechanistically, LSF suppresses chondrocyte senescence through the mTOR axis, orchestrating the equilibrium between chondrocyte anabolism and catabolism, ultimately leading to reduced apoptosis and decelerated OA cartilage degradation. LSF holds significant promise as a therapeutic approach for OA treatment, offering new insights into potential treatments for this prevalent age-related condition.

Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis

Osteoarthritis (OA) is characterised by an irreversible degeneration of articular cartilage. Here we show that the BMP-antagonist Gremlin 1 (Grem1) marks a bipotent chondrogenic and osteogenic progenitor cell population within the articular surface. Notably, these progenitors are depleted by injury-induced OA and increasing age. OA is also caused by ablation of Grem1 cells in mice. Transcriptomic and functional analysis in mice found that articular surface Grem1-lineage cells are dependent on Foxo1 and ablation of Foxo1 in Grem1-lineage cells caused OA. FGFR3 signalling was confirmed as a promising therapeutic pathway by administration of pathway activator, FGF18, resulting in Grem1-lineage chondrocyte progenitor cell proliferation, increased cartilage thickness and reduced OA. These findings suggest that OA, in part, is caused by mechanical, developmental or age-related attrition of Grem1 expressing articular cartilage progenitor cells. These cells, and the FGFR3 signalling pathway that sustains them, may be effective future targets for biological management of OA.

Adipose-Derived Stromal Vascular Fraction in Treatment of Osteoarthritis: Experimental Study

Background Osteoarthritis OA is the commonest musculoskeletal disabling disease in adults. Most of the current available treatments provide only symptomatic relief. Adipose derivedstromal vascular fraction SVF has been recently introduced as potential regenerative therapy for OA. Objective We aimed to study the therapeutic role of adipose – derived SVF in OA. Materials and Methods This work included 42 female Wister rats for induction of osteoarthritis and 6 male Wistar rats acting as donors for the extraction of SVF from adipose tissue which yielded 106 cells/ml. Osteoarthritis was induced by intra-articular injection of collagenase type II in the right knee joint of all female rats and the left knee was considered as healthy controls. Rats were divided into three groups, healthy control Group (group I), induced osteoarthritis control group (Group II) which received no treatment and SVF treatment group (Group III). Group II and III were subdivided into 2 subgroups; IIa, IIb and IIIa, IIIb which were euthanized after 1 and 2 months of OA induction respectively. Modified Manikin score (MS) was used to assess cartilage degeneration. Image Analysis was used to assess chondrocyte count, articular cartilage thickness and optical density in slides stained with Hematoxylin and Eosin and Safranin-O-stain. Results It was observed that MS scored highest in Group II compared to Group III and Group I (P < 0.001). After 1 month, MS in Group IIa and Group IIIa was (10.75 ± 0.50 and 2.50 ± 0.53, P < 0.001). Similarly at 2 months MS was (8.50 ± 0.58, 0.50 ± 0.53, P < 0.001). Also, morphometric analysis revealed Group II contained least chondrocyte cellular count compared to Group III and Group I (P < 0.001). After 2 months, articular cartilage thickness was least in Group II compared to Group IIIb and highest in Group I (P < 0.001). Also, optical density OD measurement using imaging in slides stained with Safranin revealed OD was highest in Group I, followed by Group III and least in Group II (P < 0.001). Conclusion Adipose derived SVF represents potential regenerative therapy for OA. It decreased development of degenerative changes at early stages of induced osteoarthritis in rats and promoted regeneration with increased cartilage thickness and proteoglycan content at later stage.

Adeno-Associated Virus-Delivered Fibroblast Growth Factor 18 Gene Therapy Promotes Cartilage Anabolism.

To determine the characterization of chondrogenic properties of adeno-associated virus type 2 (AAV2)-delivered hFGF18, via analysis of effects on primary human chondrocyte proliferation, gene expression, and in vivo cartilage thickness changes in the tibia and meniscus. Chondrogenic properties of AAV2-FGF18 were compared with recombinant human FGF18 (rhFGF18) in vitro relative to phosphate-buffered saline (PBS) and AAV2-GFP negative controls. Transcriptome analysis was performed using RNA-seq on primary human chondrocytes treated with rhFGF18 and AAV2-FGF18, relative to PBS. Durability of gene expression was assessed using AAV2-nLuc and in vivo imaging. Chondrogenesis was evaluated by measuring weight-normalized thickness in the tibial plateau and the white zone of the anterior horn of the medial meniscus in Sprague-Dawley rats. AAV2-FGF18 elicits chondrogenesis by promoting proliferation and upregulation of hyaline cartilage-associated genes, including COL2A1 and HAS2, while downregulating fibrocartilage-associated COL1A1. This activity translates to statistically significant, dose-dependent increases in cartilage thickness in vivo within the area of the tibial plateau, following a single intra-articular injection of the AAV2-FGF18 or a regimen of 6 twice-weekly injections of rhFGF18 protein relative to AAV2-GFP. In addition, we observed AAV2-FGF18-induced and rhFGF18-induced increases in cartilage thickness of the anterior horn of the medial meniscus. Finally, the single-injection AAV2-delivered hFGF18 offers a potential safety advantage over the multi-injection protein treatment as evidenced by reduced joint swelling over the study period. AAV2-delivered hFGF18 represents a promising strategy for the restoration of hyaline cartilage by promoting extracellular matrix production, chondrocyte proliferation, and increasing articular and meniscal cartilage thickness in vivo after a single intra-articular injection.

Intra-articular Treatment with Triamcinolone Hexacetonide Associated with Gold Nanoparticles Reduces Cartilage Degeneration in an Animal Model of Osteoarthritis.

The association between triamcinolone hexacetonide (TH) and gold nanoparticles (GNPs) represents a promising treatment due to the potential anti-inflammatory and antioxidant effects of these compounds. In this study, we evaluated the effects of intra-articular treatment of TH associated with GNPs in a mechanical model of osteoarthritis (OA). Fifty Wistar rats were divided into five groups: Sham; OA; OA+TH; OA+GNPs; OA+TH-GNPs. Both applications were performed 30 and 60 days after the model was induced. After 30 days of the last application, the animals were euthanized. Only the combined treatment with TH and GNPs promoted a reduction in proinflammatory cytokines and an increase in anti-inflammatory cytokines. The OA+TH-GNPs group obtained a significant reduction in the production of oxidants and oxidative damage markers while an increase in antioxidants. Histologically, all treated groups showed results of a significant increase in cartilage thickness and chondrocyte count, the OA+TH-GNPs group had similar behavior to the group without osteoarthritis, with significantly smaller amounts of chondrocytes than the OA group. The intra-articular use of TH associated with GNPs may be able to prevent the progression of the pathology and minimize joint degradation.

Early patellofemoral cartilage and bone pathology in a rat model of noninvasive anterior cruciate ligament rupture

ABSTRACT Objective Anterior cruciate ligament rupture (ACLR) is a risk factor for the development of post-traumatic osteoarthritis (PTOA). While PTOA in the tibiofemoral joint compartment is well-characterized, very little is known about pathology in the patellofemoral compartment after ACL injury. Here, we evaluated the extent to which ACLR induces early patellofemoral joint damage in a rat model. Methods Adult female Lewis rats were randomized to noninvasive ACLR or Sham. Two weeks post-injury, contrast-enhanced micro-computed tomography (µCT) of femoral and patellar cartilage was performed using 20% v/v ioxaglate. Morphometric parameters of femoral trochlear and patellar cartilage, subchondral bone, and trabecular bone were derived from µCT. Sagittal Safranin-O/Fast-Green-stained histologic sections were graded using the OARSI score in a blinded fashion. Results Cartilage and bone remodelling consistent with an early PTOA phenotype were observed in both femoral trochleas and patellae. ACLR caused osteophyte formation of the patella and pathology in the superficial zone of articular cartilage, including surface fibrillation, fissures, increased cellularity, and abnormal chondrocyte clustering. There were significant increases in thickness of patellar and trochlear cartilage. Loss of subchondral bone thickness, bone volume fraction, and tissue mineral density, as well as changes to patellar and trochlear trabecular microarchitecture, were indicative of catabolic bone remodelling. Several injury-induced changes, including increased cartilage thickness and trabecular spacing and decreased trabecular number were more severe in the patella compared to the trochlea. Conclusion The patellofemoral joint develops mild but evident pathology in the early period following ACL rupture, extending the utility of this model to the study of patellofemoral PTOA.

Anabolic Response of Intermittent Parathyroid Hormone and Alendronate on the Osteochondral Tissue of TMJ.

To characterize the effects of parathyroid hormone (PTH) and alendronate (Alend) on the osteochondral tissue of temporomandibular joint (TMJ). Ninety-six male and female transgenic reporter mice, 4 to 5 weeks old were divided into 6 groups: (1) Control group: Saline was injected daily for 14 days; (2) PTH: PTH was injected daily for 14 days; (3) Alend: Alend was injected every alternate days for 14 days; (4) Combined PTH and Alend: PTH was injected daily and Alend injected every alternate days for 14 days; (5) PTH then Alend: PTH was injected daily for 14 days followed by Alend injections in alternate days for 14 days; and (6) PTH wait Alend: PTH was injected daily for 14 days. There was a waiting period of 1 week before administration of Alend in alternate days for 14 days. Mice were injected with 5-ethnyl-2'-deoxyuridine (EdU), 48 and 24 hours prior to euthanization. There was significant increase in bone volume and decrease in osteoclastic activity in groups in which Alend was administered after PTH in both gender. There was significant increase in cartilage thickness with PTH or Alend alone in females, whereas in males, PTH alone led to increase in cartilage thickness. Chondrocyte apoptosis was significantly decreased with PTH or Alend alone in both male and female. Matrix metallopeptidase 13, and aggreganase-2 (ADAMTS5) expression were significantly decreased with PTH and Alend alone in both gender. PTH and Alend administration causes anabolic effects in the osteochondral tissue of TMJ.

Sprifermin for Treatment of Osteoarthritis: Recombinant Fibroblast Growth Factor 18 as a Possible Disease-Modifying Knee Osteoarthritis Drug

Osteoarthritis (OA) is a major cause of pain and disability in adults, affecting approximately 150 million people worldwide. It is most prevalent in knees and hips. Major risk factors are age, female sex, prior joint injury, and obesity. OA causes significant personal and steeply rising socio-economical costs in ageing populations. OA is characterized by progressive cartilage damage and inflammation. In later stages, it affects the subchondral bone, bone marrow, ligaments, tendons, and nerves und eventually leads to joint failure. Symptoms include pain, joint swelling, and stiffness. Therapies are symptomatic and focus on pain relief and measures to improve mobility, or, ultimately, joint replacement. So far, no drugs that could prevent or slow down disease progression are available. Based on promising in vitro and preclinical studies, recombinant fibroblast growth factor (FGF) 18 (sprifermin; Merck Serono) has come into focus as a potential disease-modifying OA drug (DMOAD). Three randomized controlled trials (RCTs) investigating the safety and efficacy of intraarticularly (i.a.) injected sprifermin application in patients with knee OA have been completed so far. Data from these trials, post hocanalyses and follow-ups provide have evidenced that i.a. sprifermin induced a significant and sustained increase in cartilage thickness and volume without specific adverse effects, but in terms of clinical symptoms or physical joint function sprifermin did not cause significant improvements compared to placebo treatment in whole study populations. However, significant pain reduction was observed in a “subgroup at risk” of patients with more severe disease states, indicating that under certain disease conditions the structural benefit improvements could translate into clinical benefit. This calls for larger RCTs allowing e.g., for disease state or risk factor-specific stratification of patients and longer follow-ups to substantiate the efficacy of sprifermin as a possible DMOAD. This review gives an overview on the prevalence, etiology and socio-economic burden of OA, its pathogenesis as well as the current treatment options of the disease. It summarizes the role of FGF-18 in chondrocyte and cartilage (patho)physiology and addresses the question of evidence for the efficacy and safety of i.a. sprifermin injection in patients with knee OA based on trial outcomes and literature data.

Optimization of the Duration of the Administration of Mesenchymal Stem Cells Wharton’s Jelly to the Level of Matrix Metalloproteinase-1 and Transforming Growth Factor-β in Osteoarthritis Rat Model

BACKGROUND: Mesenchymal Stem Cell Wharton’s Jelly (MSC-WJ) is promising candidates for osteoarthritis (OA) therapy since they have chondrogenic potential and the ability to form the extracellular matrix. AIM: This study aimed to determine the effect of the time giving MSC-WJ on bioactive markers of osteoarthritis. METHODS: The osteoarthritis rat model was treated by intra-articular injection with MSC-WJ and α _MEM as a control. Four and 8 weeks later performed a histological analysis of cartilage and the determination of the levels of Matrix Metalloproteinase-1(MMP-1) and Transforming growth factor β1 (TGF-β1) in serum by ELISA. RESULTS: The results showed that administration of MSC-WJ showed improvement in the histological picture of knee joints in experimental animals characterized by an increase in cartilage thickness on the joint surface. The administration of MSC-WJ showed a tendency to decrease MMP-1 serum levels of OA rats treated for 8 weeks, although statistically did not show a significant difference. Whereas, administration of MSC-WJ showed a decrease in serum levels of TGF-β1 OA rat treated for 8 weeks. CONCLUSION: MSC-WJ can repair damaged knee OA cartilage tissue. The administration of MSC-WJ can reduce serum levels of TGF-β1 OA rats treated for 8 weeks.

Local estrogen for nonsurgical recontouring of auricular cartilage

5% of children are born with auricular deformities. Permanent recontouring can be achieved through splinting during early infancy. Beyond this time, splinting is ineffective, and patients require surgical correction. Neonatal cartilage malleability is hypothesized to be secondary to retained maternal estrogens, increasing hyaluronic acid concentration. In this article, we evaluate the efficacy of local estrogen treatments for the nonsurgical recontouring of mature auricular cartilage. Ears of New Zealand rabbits were folded and splinted and then were randomly assigned to an experimental group, n=10 (injected estrogen, topical estrogen, saline, or untreated). Treatment ears received injected estrogen or saline twice weekly or topical estrogen daily for 4 weeks. Two weeks post-treatment, splints were removed, and ear angles were measured. Biopsies were taken for histologic and mechanical analysis, and systemic estrogen levels were assayed. Ear angles stabilized by 9 days post-splinting. Topical estrogen led to a significantly smaller resting angle (121.6° ± 13.5°) compared with saline and control (135.9° ± 11.2° and 145.3° ± 13.0°, respectively). Injected estrogen led to the most pronounced angle decrease (64.5° ± 35.3°). Ears injected with estrogen also showed a significant increase in cartilage thickness. Hyaluronic acid concentration was increased in both estrogen treatment groups compared with saline. At 3 weeks post-treatment, there was no significant differences in the elastic modulus of the cartilage or serum estrogen levels among the groups. Results show the potential result of local estrogen treatment to achieve a stable nonsurgical remodeling of mature auricular cartilage. Further study is needed to evaluate the molecular mechanism and improve the transdermal estrogen delivery to optimize treatment regimen.

Ultrasonographic Evaluation of the Metacarpal Cartilage Thicknesses in Weightlifters and Volleyball Players.

The aim of the study was to evaluate the possible effects of impact and loading on the metacarpal cartilage and hand functions in young elite athletes. In this cross-sectional study athletes with at least 3 yrs of sport background and who have been under a scheduled training program were enrolled. The second to fifth fingers' metacarpal head cartilage thicknesses were measured bilaterally by using ultrasonography. Handgrip and pinch strengths were measured. Michigan Hand Outcomes Questionnaire was also completed for every participant. A total of 42 male athletes (19 weightlifters, 23 volleyball players) and 46 healthy control subjects were enrolled. Metacarpal cartilage thicknesses of the athletes were thicker than those of the healthy controls (all P < 0.001). There were no differences between the dominant and nondominant hands (all P > 0.05). In the weightlifting group, Michigan Hand Outcomes Questionnaire work performance and pain scores were worse than the other groups (both P < 0.001). The presence of increased cartilage thickness measurements in the athletes suggests that sports activities might affect the metacarpal articular cartilage. Highest pain scores and lowest work performance scores in the weightlifters with highest metacarpal cartilage thickness might suggest that impact and loading during their sports play could lead to cartilage edema.

EXPLORING GENDER‐DEPENDENT DIFFERENCES IN PATTERNS OF CARTILAGE LOSS USING RESPONSIVENESS HEAT MAPS: DATA FROM THE OAI

Understanding gender-specific differences in patterns of cartilage loss can improve our knowledge of the pathogenesis of knee osteoarthritis (KOA) development and progression and may inform clinical trials of treatments for KOA. Quantitative cartilage assessment using segmentation software offers an ideal method for appreciating these patterns. The goal of our study was to examine gender differences in patterns of cartilage loss in the central weight-bearing regions of the medial femur (MF), lateral femur (LF), medial tibia (MT), and lateral tibia (LT) using cartilage segmentation software. We measured cartilage volume change in the indexed knee of 480 subjects with Kellgren-Lawrence (KL) 2 and 3 from the OAI at the baseline (BL) and 96-month (mo) time points using the local area cartilage segmentation (LACS) method. Briefly, the LACS method uses robust coordinate systems fixed to anatomical landmarks to find the cartilage volume or thickness in consistent sub-regions on each cartilage plate. (See Figure 1.) Using the coordinate systems, LACS permits assessment of change in much smaller sub-regions through the use of responsiveness heat maps. The average age, BMI, and KL score were 59.5years, 28.7kg/m 2 , 2.03 (males) and 60.5years, 28.8kg/m 2 , 1.99 (females). Figure 2 shows heat map images of the change in cartilage volume from BL to 96mo for males and females. The intensity of the colors (red for loss, blue for gain) represents the standardized response mean (SRM) value at each location. We observed more focused thinning for females in the lateral/posterior portion of the MF and the medial side of the LT. An increase in cartilage thickness in the posterior side of the LF sub-region was also observed for females, as shown with the blue area. Similar patterns were observed for other follow-up time points (i.e., BL to 24mo, BL to 48mo, and BL to 72mo) and when stratifying by age, BMI and KL score. Heat maps of smaller subregions were capable of illustrating gender-specific differences in patterns of cartilage loss, differences that may offer insight into the variation of gender differences in the natural history of KOA. Heat maps of cartilage thickness changes may be useful in evaluating the benefit of interventions for KOA. NIH AR071409 none CORRESPONDENCE ADDRESS: jduryea@bwh.harvard.edu .

Articular cartilage thickness changes differ between males and females 4 years following anterior cruciate ligament reconstruction.

Anterior cruciate ligament injury and reconstruction (ACLR) affects articular cartilage thickness profiles about the tibial, femoral, and patellar surfaces; however, it's unclear whether the magnitudes of change in cartilage thickness, as well as the locations and areas over which these changes occur, differ between males and females. This is important to consider as differences exist between the sexes with regard to knee biomechanics, patellofemoral pain, and anatomic alignment, which influence risk of an index and repeated injury. Subjects underwent ACLR with a bone-patella tendon-bone autograft. At 4-year follow-up, they had asymptomatic knees; however, significant ACL injured-to-contralateral normal knee differences in articular cartilage thickness values were observed. Both thickening and thinning of cartilage occurred about the tibiofemoral and patellofemoral joints, relative to matched control subjects with normal knees. Further, the location of the areas and magnitudes of thickening and thinning were different between females and males. Thickening (swelling) of articular cartilage is an early finding associated with the onset of posttraumatic osteoarthritis (PTOA). Therefore, the increases in cartilage thickness that were observed in this cohort may represent early signs of the onset of PTOA that occur prior to the patient developing symptoms and radiographic evidence of this disease. The different locations of areas that underwent a change in cartilage thicknesses between males and females suggest that each sex responds differently to knee ligament trauma, reconstruction, rehabilitation, and return to activity, and indicates that sex-specific analysis should be utilized in studies of PTOA.

POS1091 KNEE JOINT DISTRACTION RESULTS IN MRI CARTILAGE THICKNESS INCREASE UP TO TEN YEARS AFTER TREATMENT

Background:Knee joint distraction (KJD) is a joint-preserving treatment option for younger (age &lt;65 years) knee osteoarthritis (OA) patients. It has shown clinical improvement for up to nine years after treatment. Radiographs and MRI scans have previously shown cartilage regeneration activity, especially in the first two years after treatment. However, MRIs have not been evaluated more than five years after this treatment.Objectives:To evaluate MRI cartilage thickness up to ten years after KJD treatment.Methods:Patients (n=20) with end-stage knee OA, indicated for total knee arthroplasty (TKA) but &lt;60 years old, were treated with KJD. 3T MRIs with 3D spoiled gradient recalled imaging sequence with fat suppression (SPGR-fs) were acquired before and one, two, five, seven and ten years after surgical treatment. Stradview v6.0 was used for semi-automatic cartilage segmentation; wxRegSurf v18 was used for surface registration. MATLAB R2020a and the SurfStat MATLAB package were used for data analysis and visualization. For changes over time, linear mixed models were used. Two separate linear regression models were used to show the influence of baseline Kellgren-Lawrence grade and sex on the changes over time. Statistical significance was calculated with statistical parametric mapping; a p-value &lt;0.05 was considered statistically significant. Since KJD has previously shown significant results mostly in the patients’ most affected compartment (MAC), patients were separated in two groups based on whether their MAC was the medial or lateral compartment.Results:The MAC was predominantly the medial side (medial MAC n=18; lateral n=2). The 18 patients with a medial MAC all had MRI scans at baseline, one and two years after treatment. After two years, some patients were lost to follow-up, decreasing data availability at five (n=15), seven (n=11) and ten years (n=7). Figure 1 (top) shows the average cartilage thickness at the different time points for all medial MAC patients together. One and two years after treatment the cartilage in the medial weight-bearing region was on average thicker than before treatment. While from five years after treatment the cartilage thickness gradually decreased, even at ten years the medial cartilage thickness seemed slightly higher than pre-treatment. Figure 1 (bottom) shows cartilage thickness changes compared to baseline for patients with a medial MAC. Patients with a lateral MAC showed a similar pattern, with the biggest changes showing on the lateral side. As indicated by the dark blue areas, the medial femoral cartilage thickness increase, which was up to 0.5 mm after one year and 0.6 mm after two years, was largely statistically significant at both these time points. While the medial tibia showed an increase of up to 0.5 mm at these time points as well, this was not statistically significant at two years. Surprisingly, long-term results showed areas of the lateral (less affected) compartment were significantly thicker, up to 0.7 mm, compared to pre-treatment in both the femur and tibia compared to baseline. Kellgren-Lawrence grade and sex were shown to influence the changes, albeit not statistically significantly. Patients with a higher Kellgren-Lawrence grade and male sex showed a higher short-term (one and two year) but a lower long-term (seven and ten year) cartilage thickness increase.Conclusion:KJD treatment results in significant short-term cartilage regeneration in the most affected compartment. While after two years this initial gain in cartilage thickness is gradually lost, likely as a result of natural progression, even ten years after treatment the cartilage is thicker than before treatment. In the less affected compartment, a delayed cartilage response seems to take place, with significantly increased cartilage thickness in the long term. In conclusion, in these young OA patients indicated for TKA, KJD results in femoral and tibial cartilaginous tissue regeneration both short- and long-term and in both sides of the joint.Disclosure of Interests:None declared.

Histomorphometric Quantitative Evaluation of Long-Term Risedronate Use in a Knee Osteoarthritis Rabbit Model.

Osteoarthritis (OA) treatment is a major orthopedic challenge given that there is no ideal drug capable to reverse or stop the progression of the OA. In that regard, bisphosphonates have been proposed as potential disease-modifying drugs due to their possible chondroprotective effect related to obtaining a greater subchondral bone quality. However, their effectiveness in OA is still controversial and additionally, there is little evidence focused on their long-term effect in preclinical studies. The aim of this study was to evaluate the risedronate quantitative effect on articular and subchondral periarticular bone by histomorphometry, in an experimental rabbit model in an advanced stage of OA. Twenty-four adult New Zealand rabbits were included in the study. OA was surgically induced in one randomly chosen knee, using the contralateral as healthy control. Animals were divided into three groups (n = 8): placebo control group, sham surgery group and risedronate-treated group. After 24 weeks of treatment, cartilage and subchondral femorotibial pathology was evaluated by micro-computed tomography (micro-CT) and undecalcified histology. The research results demonstrated that the experimental animal model induced osteoarthritic changes in the operated joints, showing an increased cartilage thickness and fibrillation associated with underlying subchondral bone thinning and decreased trabecular bone quality. These changes were especially highlighted in the medial tibial compartments as a possible response to surgical instability. Regarding the trabecular analysis, significant correlations were found between 2D histomorphometry and 3D imaging micro-CT for the trabecular bone volume, trabecular separation, and the trabecular number. However, these associations were not strongly correlated, obtaining more precise measurements in the micro-CT analysis. Concerning the long-term risedronate treatment, it did not seem to have the capacity to reduce the osteoarthritic hypertrophic cartilage response and failed to diminish the superficial cartilage damage or prevent the trabecular bone loss. This study provides novel information about the quantitative effect of long-term risedronate use on synovial joint tissues.

Subregional anatomical prevalence of cartilage damage in knees with radiographic disease severity Kellgren-Lawrence 2 and 3: the most study

Purpose: Imaging plays an important role in defining structural disease severity and potential suitability of patients recruited to disease-modifying osteoarthritis drug (DMOAD) trials. A common target tissue of DMOADs is cartilage and structural success of a clinical trial is usually defined by reduced cartilage loss or increase in cartilage thickness compared to placebo, commonly in the medial tibio-femoral joint (TFJ). To be eligible for inclusion into a DMOAD trial from a structural perspective, knees with Kellgren-Lawrence (KL) grades 2 and 3 are typically included.

Heterogeneity of cartilage involvement in knees with radiographic disease severity Kellgren-Lawrence 2 and 3: the most study

Purpose: Imaging plays an important role in defining structural disease severity and potential suitability of patients recruited to disease-modifying osteoarthritis drug (DMOAD) trials. A common target tissue of DMOADs is cartilage and structural success of a clinical trial is usually defined by reduced cartilage loss or increase in cartilage thickness compared to placebo, commonly in the medial tibio-femoral joint (TFJ). To be eligible for inclusion into a DMOAD trial from a structural perspective, knees with Kellgren-Lawrence (KL) grades 2 and 3 are typically included.

Study of changes in rat mandibular condyle under intermittent cyclic and continuous compressive stress

ObjectivesThis study aimed to investigate the effects of intermittent and continuous compressive stress on rat mandibular condyles. DesignNinety rats were randomly divided into 5 groups: non-loading control groups and 1-day intermittent cyclic loading, 3-day intermittent cyclic loading, 7-day intermittent cyclic loading, continuous loading groups. In the loading groups, compressive mechanical stresses were loaded onto the condyles. The rats were euthanized after one, two, or four weeks. Histomorphometric and immunochemical staining of the cartilage and the micro-CT scanning of subchondral bone were investigated. ResultsUnder continuous loading following the first week, cartilage thickness, numbers of chondrocytes, extracellular matrix (Type-II collagen) and proliferation decreased significantly, and there was no apparent repair response after the second and fourth weeks. The cartilage of 1-day and 3-day intermittent cyclic loading groups showed similar pathological changes but better proliferative activity compared with the continuous loading group. The 7-day intermittent loading group had significant recovery after 2 weeks, including the increase of cartilage thickness and the number of chondrocytes, cell swelling and rearranging. However, the remodeling of subchondral bone showed no significant difference between the intermittent and continuous loading stress compared to the control group. ConclusionsUnder moderate mechanical stress, the condylar cartilage actively remodeled, whereas the subchondral bone, as supportive rigid structure, was less sensitive to mechanical pressure. The intermittent compressive stress protects the condylar cartilage from excessive damage, which is different from continuous compressive stress. With longer intervals, the cartilage has the potential capability for recovery as the initial state.

Does Intra-Articular Injection of Platelet-Rich Plasma Have an Effect on Cartilage Thickness in Patients with Primary Knee Osteoarthritis?

To determine the effect of intra-articular injection of platelet-rich plasma (PRP) in patients with primary knee osteoarthritis (OA) by clinical evaluation and ultrasonographic (US) assessment of cartilage thickness. A total of 100 patients with mild to severe primary knee OA using the Kellgren- Lawrence (K-L) grading scale were included and divided into two groups. Group I included 50 patients who were given two intra-articular knee injections of PRP, 1 week apart; Group II included 50 patients who received non-steroidal anti-inflammatory drugs (NSAIDs) and chondroprotective drugs. Functional assessment of all OA patients was done using the basal WOMAC score, at 2 and 6 months. US assessment of femoral condylar cartilage thickness was conducted basally and at 6 months. Improvement of WOMAC score was observed at 2 and 6 months in Group I following PRP injection compared to Group II (p values < 0.001), The improvement of WOMAC in Group I occurred in all severity degrees of OA (p < 0.001). Moreover, a significant increase in cartilage thickness was found at the intercondylar area (ICA) at 6 months relative to baseline assessment by US in Group I (p = 0.041). Treatment with PRP injections can reduce pain and improve knee function in patients with various degrees of articular degeneration. Further studies are needed to clarify the anabolic effect of PRP on the articular cartilage.