Early Cartilage Degeneration Research Articles

Association of Preoperative Cartilage T1ρ Values With Progression of Knee Osteoarthritis 10 Years After Anatomical Double-Bundle ACL Reconstruction: Follow-up of a Previous Prospective Study.

The factors contributing to osteoarthritis progression after anterior cruciate ligament (ACL) injury and reconstruction (ACLR) are not fully understood. Quantitative magnetic resonance imaging (MRI) offers a noninvasive way to evaluate cartilage biochemical composition using T1ρ mapping, thereby detecting early cartilage degeneration. The specific impact of preoperative quantitative MRI on long-term outcomes after ACLR remains underreported. The purpose of this study was to investigate the effects of various factors, including preoperative cartilage T1ρ values, on the 10-year outcomes after ACLR. It was hypothesized that individual differences in baseline cartilage degeneration would influence osteoarthritis progression at 10 years postoperatively. Case series; Level of evidence, 4. This case series involved 13 patients with primary ACL injury who underwent anatomical double-bundle ACLR using hamstring tendon autograft between April 2012 and August 2013. All patients underwent preoperative quantitative MRI using a 3.0-T scanner with an 8-channel knee coil. Cartilage was divided into 18 compartments for compositional analysis, and average T1ρ values were calculated for each compartment. At the 10-year follow-up, 9 of the patients were available for patient-reported outcome (PRO) measures and radiographs. The 9 patients (6 female, 3 male) had a mean age of 26.4 years and a mean body mass index of 23.3 at surgery. All patients exhibited favorable PRO scores at the 10-year follow-up, but 5 patients showed osteoarthritis progression according to Kellgren-Lawrence (KL) grade. Although preoperative T1ρ values did not significantly correlate with PRO scores, patients with KL grade progression had significantly higher preoperative T1ρ values in the posterolateral tibial cartilage than those without progression (P = .04). Ten years after anatomical double-bundle ACLR, most patients reported favorable outcomes. Preoperative T1ρ values were not directly correlated with PROs, although the presence of a patient subset with progressive KL grades suggests that preoperative posterolateral tibial cartilage condition may influence long-term osteoarthritis progression.

Concurrent Joint Contact in Anterior Cruciate Ligament Injury induces cartilage micro-injury and subchondral bone sclerosis, resulting in knee osteoarthritis.

Anterior Cruciate Ligament (ACL) injury initiates post-traumatic osteoarthritis (PTOA) via two distinct processes: initial direct contact injury of the cartilage surface during ACL injury, and secondary joint instability due to the ACL deficiency. Using the well-established Compression-induced ACL rupture method (ACL-R) and a novel Non-Compression ACL-R model, we aimed to reveal the individual effects of cartilage compression and joint instability on PTOA progression after ACL injury in mice. Twelve-week-old C57BL/6J male were randomly divided to three experimental groups: Compression ACL-R, Non-Compression ACL-R, and Intact. Following ACL injury, we performed joint laxity testing and microscopic analysis of the articular cartilage surface at 0 days, in vivo optical imaging of matrix-metalloproteinase (MMP) activity at 3 and 7 days, and histological and microCT analysis at 0, 7, 14, and 28 days. The Compression ACL-R group exhibited a significant increase of cartilage roughness immediately after injury compared with the Non-Compression group. At 7 days, the Compression group exhibited increased MMP-induced fluorescence intensity and MMP-13 positive cell ratio of chondrocytes. Moreover, histological cartilage degeneration was observable in the Compression group at the same time point. Sclerosis of tibial subchondral bone in the Compression group was more significantly developed than in the Non-Compression group at 28 days. Both Compression and Non-Compression ACL injury initiated PTOA progression due to joint instability. However, joint contact during ACL rupture also caused initial micro-damage on the cartilage surface and initiated early MMP activity, which could accelerate PTOA progression compared to ACL injury without concurrent joint contact.

A feasibility study of in vivo quantitative ultra-short echo time-MRI for detecting early cartilage degeneration

ObjectivesTo explore the feasibility of Ultra-short echo time (UTE) – MRI quantitative imaging in detecting early cartilage degeneration in vivo and underlying pathological and biochemical basis.MethodsTwenty volunteers with osteoarthritis (OA) planning for total knee arthroplasty (TKA) were prospectively recruited. UTE-MRI sequences and conventional sequences were performed preoperatively. Regions of interests (ROIs) were manually drawn on the tibial plateau and lateral femoral condyle images to calculate MRI values. Cartilage samples were collected during TKA according to the preset positions corresponding to MR images. Pathological and biochemical components of the corresponding ROI, including histological grading, glycosaminoglycan (GAG) content, collagen integrity, and water content were obtained.Results91 ROIs from volunteers of 7 males (age range: 68 to 78 years; 74 ± 3 years) and 13 females (age range: 57 to 79 years; 67 ± 6 years) were evaluated. UTE-MTR (r = −0.619, p < 0.001), UTE-AdiabT1ρ (r = 0.568, p < 0.001), and UTE-T2* values (r = −0.495, p < 0.001) showed higher correlation with Mankin scores than T2 (r = 0.287, p = 0.006) and T1ρ (r = 0.435, p < 0.001) values. Of them, UTE-MTR had the highest diagnostic performance (AUC = 0.824, p < 0.001). UTE-MTR, UTE-AdiabT1ρ and UTE-T2* value was mainly related to collagen structural integrity, PG content and water content, respectively (r = 0.536, −0.652, −0.518, p < 0.001, respectively).ConclusionUTE-MRI have shown greater in vivo diagnostic value for early cartilage degeneration compared to conventional T2 and T1ρ values. Of them, UTE-MTR has the highest diagnostic efficiency. UTE-MTR, UTE-AdiabT1ρ, and UTE-T2* value mainly reflect different aspects of cartilage degeneration--integrity of collagen structure, PG content, and water content, respectively.Critical relevance statementUltra-short echo time (UTE)-MRI has the potential to be a novel image biomarkers for detecting early cartilage degeneration in vivo and was correlated with biochemical changes of early cartilage degeneration.Key PointsConventional MR may miss some early cartilage changes due to relatively long echo times.Ultra-short echo time (UTE)-MRI showed the ability in identifying early cartilage degeneration in vivo.UTE-MT, UTE-AdiabT1ρ, and UTE-T2* mapping mainly reflect different aspects of cartilage degeneration.Graphical

Activatable theranostic nanoprobes for Fluorescence/MR imaging and microenvironment remodeling of early cartilage degeneration

Osteoarthritis (OA) is a degenerative joint disease of the knee joint, suffering from the limited therapeutic effect and serious side effects. Unfortunately, there are currently rarely available materials to fundamentally delay and monitor OA progression. The OA microenvironment, including excessive inflammation, matrix metalloproteinases (MMPs), oxidative stress, and reactive oxygen species (ROS), play a crucial role in the pathogenesis of OA. Utilizing and remodeling OA microenvironment may be an effective strategy for the diagnosis and treatment of OA. This work developed an intelligent responsive nanoprobe, Gd-HMPB@SMT@MMP (GHPSM) by encapsulating S-methylisothiourea (SMT) loaded mesoporous Prussian Blue (Gd-HMPB) with Tetramethyl Rhodamine (TAMRA) labeled MMP-13 peptide (MMP-13-TAMRA) for this aim. GHPSM displayed enhanced accumulation in OA cartilage site due to the decrease in the content of negatively charged aminoglycans (GAGs) in early degenerative articular cartilage and activated fluorescence signal as well as SMT controlled release due to the cleavage of MMP-13-TAMRA from GHPSM by overexpressed MMP-13 matrix protease in OA microenvironment. Furthermore, integrating the function of SMT and PB nanozyme, GHPSM reshaped the OA microenvironment by reducing the release of ROS and inflammatory factors (TNF-α, IL-6, iNOS), increasing the expression of intermediate structural proteins (COL2 and Aggrescan), thereby reducing cartilage degradation and chondrocyte apoptosis, ultimately delaying the development of OA. The progressions of early OA disease after different treatments were successfully tracked based on fluorescence/MR imaging with X-ray imaging of knee joint for comparation. These findings highlight the potentials of GHPSM in monitoring the status of cartilage in real-time and delay OA progression by reshaping the OA microenvironment, providing novel ideas for future research in OA diagnosis and treatment.

The value of adding T2 mapping sequence to the routine MRI protocol in the evaluation of cartilage lesions of the ankle joint

BackgroundAnkle joint cartilage injury is frequently associated with degenerative changes, even in the absence of symptoms. Earlier treatment of cartilage damage with joint preservation is clearly more successful. The main limitation of morphologic cartilage magnetic resonance imaging sequences is that they are not very sensitivity in the detection of early cartilage degeneration. Recent advances in biochemical magnetic resonance imaging have yielded sequences that are sensitive to molecular changes in the composition of cartilage matrix. This includes water- and collagen-sensitive T2\\T2* mapping. The aim of this study was to determine the extent of improvement of the diagnostic performance of routine magnetic resonance imaging protocol in the evaluation of ankle joint articular cartilage lesions following the addition of a T2 mapping sequence.ResultsA total of 45 cases, 30 patients (12 male and 18 female) and 15 controls (10 male and 5 female) who underwent routine ankle magnetic resonance imaging with additional T2 mapping sequence, were included in the study. Out of 30 patients, four patients were misdiagnosed as being normal, while having changes of cartilage composition of early degenerative changes, discovered by T2 mapping sequence. The patients group as well as the-control groups had significantly higher T2-values in the superficial cartilage layer (P < 0.001) compared to the deep layer. When comparing between the medial and the lateral compartments at patients group, the T2-relaxation times were more pronounced in the medial talar cartilage compartment compared to the lateral talar cartilage compartment.ConclusionsMagnetic resonance imaging can observe not only the destruction of the structural integrity but also the change of the components in articular cartilage. In this study, the addition of a T2 mapping of the ankle cartilage sequence to a routine MR ankle protocol improved sensitivity and accuracy in the detection of early cartilage lesions within the ankle joint.

Quadriceps and Hamstrings Activation Peaks Earlier as Athletes Repeatedly Hop, but There are Differences Depending on ACL Reconstruction Technique.

After Anterior Cruciate Ligament Reconstruction (ACLR) athletes face the challenge of regaining their previous competitive level while avoiding re-injury and early knee joint cartilage degeneration. Quadriceps and hamstrings strength reductions and neuromuscular alterations potentially related to risk of re-injury are present after ACLR and relate to deficits in muscle activation. Cross-sectional laboratory study. To examine quadriceps and hamstrings muscle activation during repeated hops in healthy pivoting-sport athletes and those who had undergone ACLR (bone-tendon-bone and semitendinosus graft) who had met functional criteria allowing return to training. Surface electromyography (SEMG) was recorded from vastus medialis and lateralis and medial and lateral hamstrings bilaterally during 30 seconds' repeated hopping in male athletes on average eight months after ACLR surgery (5-12 months). All patients underwent hamstring (HS) (n=24) or bone-tendon-bone (BTB) reconstruction (n=20) and were compared to healthy controls (n=31). The SEMG signals were normalized to those obtained during maximal voluntary isometric contraction. A significant time shift in peak muscle activation (earlier) was seen for: vastus medialis and vastus lateralis activation in the control group, in the BTB group's healthy (but not injured) leg and both legs of the HS group. A significant time shift in peak muscle activation was seen for lateral hamstrings (earlier) in all but the BTB group's injured leg and the medial hamstrings in the control group only. Lower peak activation levels of the vastus lateralis (p\<0.001) and vastus medialis (p\<0.001) were observed in the injured compared to healthy legs and lower peak lateral hamstrings activity (p\<0.009) in the injured leg compared to control leg. Decline in medial hamstring peak activation (p\<0.022) was observed between 1st and 3rd phase of the hop cycle in all groups. Repeated hop testing revealed quadriceps and hamstring activation differences within ACLR athletes, and compared to healthy controls, that would be missed with single hop tests. 3.

Modulation of early osteoarthritis by tibiofemoral re-alignment in sheep

ObjectiveTo investigate whether tibiofemoral alignment influences early knee osteoarthritis (OA). We hypothesized that varus overload exacerbates early degenerative osteochondral changes, and that valgus underload diminishes early OA. MethodNormal, over- and underload were induced by altering alignment via high tibial osteotomy in adult sheep (n = 8 each). Simultaneously, OA was induced by partial medial anterior meniscectomy. At 6 weeks postoperatively, OA was examined in five individual subregions of the medial tibial plateau using Kellgren-Lawrence grading, quantification of macroscopic OA, semiquantitative histopathological OA and immunohistochemical type-II collagen, ADAMTS-5, and MMP-13 scoring, biochemical determination of DNA and proteoglycan contents, and micro-computed tomographic evaluation of the subchondral bone. ResultsMultivariate analyses revealed that OA cartilaginous changes had a temporal priority over subchondral bone changes. Underload inhibited early cartilage degeneration in a characteristic topographic pattern (P ≥ 0.0983 vs. normal), in particular below the meniscal damage, avoided alterations of the subarticular spongiosa (P ≥ 0.162 vs. normal), and prevented the disturbance of otherwise normal osteochondral correlations. Overload induced early alterations of the subchondral bone plate microstructure towards osteopenia, including significantly decreased percent bone volume and increased bone surface–to–volume ratio (all P ≤ 0.0359 vs. normal). ConclusionThe data provide high-resolution evidence that tibiofemoral alignment modulates early OA induced by a medial meniscus injury in adult sheep. Since underload inhibits early OA, these data also support the clinical value of strategies to reduce the load in an affected knee compartment to possibly decelerate structural OA progression.

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

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

Application of functional magnetic resonance imaging for evaluation of cartilage injury effect on knee joint function by recurrent patellar dislocation.

Explore the therapeutic effect of vastus medialis oblique plasty and the reliability and applicability of functional magnetic resonance imaging as a diagnostic method for early cartilage degeneration and injury diagnosis. From July 2020 to July 2022, there were 53 patients with recurrent patellar dislocation who met the inclusion criteria for surgery, including 34 women and 19 men, aged 11 to 53 years, with an average age of 24.4 years. After patient selection, functional magnetic resonance imaging was performed before surgery. According to the presence or absence of cartilage injury, they were divided into cartilage injury group (n = 28) and non-cartilage injury group (n = 25), and underwent vastus medialis oblique plasty. Preoperative patellar axial radiographs were performed in both groups of patients to measure the patellar tilt angle and lateral patellofemoral angle. The Lysholm, Kujala, and VAS (visual analogue scale) scores were applied to assess changes in knee joint function and anterior knee pain. All patients were postoperatively followed up. The patellar tilt angle and lateral patellofemoral angle of the 2 groups were significantly improved postoperatively (P < .05), with no statistical difference between the 2 groups (P > .05). Significant differences were observed in the VAS changes between the cartilage injury group and the non-cartilage injury group before and after operation (P < .05). There was a statistical difference in VAS score between the groups (P < .05). The changes in the Lysholm and Kujala scores before and after the operation in the cartilage injury and the non-cartilage injury groups were statistically different (P < .05). There was statistical difference between the 2 groups in Lysholm score and Kujala score after operation (P < .05). Vastus medialis oblique plasty significantly improved knee joint function and pain. Patients with cartilage injury had worse preoperative and postoperative knee function than patients without cartilage injury. Functional magnetic resonance imaging can reflect the early-stage changes in the biochemical cartilage components caused by recurrent patellar dislocation.

Ultra-Short Echo Time-MRI T2* Mapping of Articular Cartilage Layers Is Associated with Histological Early Degeneration.

Ultra-short TE (UTE) sequences on MRI are a technique that improves the visualization of tissues with short T2 relaxation time, such as deep cartilage layers. In addition, T2* relaxation time calculated from the UTE has the potential to evaluate water molecules bound to the cartilage matrix. This study was performed to determine if there is an association between UTE-T2* relaxation time by cartilage layer and histological degeneration in knee osteoarthritis (OA). Seven knees that had undergone total knee arthroplasty (TKA) were included in the study, and the lateral tibial cartilage, which had the least degeneration of the resected bones, was used as the sample. The T2* relaxation time of 4 patients with no abnormal findings on MRI was the reference relaxation time. Histological degeneration of TKA samples was assessed by the Mankin score and graded as the early OA group (≤3 points) and the advanced OA group (≥4 points). The association between T2* relaxation time and Mankin grade in each cartilage layer was compared. The effect of angiogenesis to the tidemark on T2* relaxation time was also compared. T2* relaxation time of the cartilage layer was significantly longer in early OA than that in the control group. In the deep cartilage layer, the mean T2* relaxation time for angiogenesis (-) was 15.7 ms, whereas it was significantly shorter for angiogenesis (+) at 8.2 ms. The UTE-T2* relaxation time was associated with histological cartilage degeneration, suggesting a potential application in monitoring early cartilage degeneration.

Poster 290: Effect of Platelet-rich Plasma Injections on Cartilage T1rho in Knee Osteoarthritis

Poster 290: Effect of Platelet-rich Plasma Injections on Cartilage T1rho in Knee Osteoarthritis

Ultrasonographic echo intensity in the medial femoral cartilage is enhanced prior to cartilage thinning in women with early mild knee osteoarthritis.

We aimed to determine whether altered cartilage echo intensity is associated with knee osteoarthritis (OA) severity and whether the alteration occurs before thinning of the femoral cartilage in knee OA. The medial femoral cartilage thickness and echo intensity of 118 women aged ≥ 50years were assessed using an ultrasound imaging device. Based on the Kellgren-Lawrence (KL) grade and knee symptoms, participants were classified into five groups: control (asymptomatic grades 0-1), early OA (symptomatic grade 1), grade 2, grade 3, and grade 4. Analysis of covariance, with adjusted age and height, and the Sidak post hoc test were used to assess the differences in cartilage thickness and echo intensity in knees with varying OA severity. The echo intensity on longitudinal images, equivalent to the tibiofemoral weight-bearing surface, was significantly higher in the grade 2 group than that in the control group (p = 0.049). However, no significant difference was noted in cartilage thickness (n.s.). In the grades 3 and 4 groups, cartilage thickness became thinner as OA progressed (p < 0.001 and p < 0.001, respectively). However, the cartilage echo intensity was not significantly enhanced compared with that of the grade 2 group (n.s.). There were no significant differences in the cartilage thickness and echo intensity between the early OA and control groups on the longitudinal images (n.s.). The echo intensity of the medial femoral cartilage was high in patients with KL grade 2, without decreased thickness. Our findings suggested that higher echo intensity is a feature of early cartilage degeneration in mild knee OA. Further studies are needed to establish this feature as a useful screening parameter of early cartilage degeneration in knee OA. Level III.

CHANGES TO LEVELS OF CHONDROCYTE-ASSOCIATED ADAMTS-4 IN EARLY HUMAN OSTEOARTHRITIS

Early changes within articular cartilage during human idiopathic osteoarthritis are poorly understood. However alterations to chondrocyte morphology occur with the development of fine cytoplasmic processes and cell clusters, potentially playing a role in cartilage degeneration. The aggrecanase ADAMTS-4 (A disintegrin and metalloproteinase with thrombospondin motifs-4) has been implicated as an important factor in cartilage degradation, so we investigated the relationship between chondrocyte morphology and levels of ADAMTS-4 in both non-degenerate and mildly osteoarthritic human cartilage.Human femoral heads were obtained following consent from patients undergoing hip arthroplasty following femoral neck fracture. Cartilage explants of normal (grade 0; G0) and mildly osteoarthritic (grade 1; G1) cartilage were labelled with the cytoplasmic dye CMFDA (5-chloromethylfluorescein-diacetate). Explants were cryosectioned (30μm sections), and labelled for ADAMTS-4 by fluorescence immunohistochemistry. Sections were imaged with confocal microscopy, allowing the semi-quantitative analysis of ADAMTS-4 and 3D visualisation of in situ cell morphology.With cartilage degeneration from G0 to G1, there was a decrease in the proportion of chondrocytes with normal rounded morphology (P&lt;0.001) but an increase in the proportion of cells with processes (P&lt;0.01) and those in clusters (P&lt;0.001;[4(1653)]; femoral heads:cells). Although average levels of ADAMTS-4 for all cells was the same between G0 and G1 (P&gt;0.05), a change was evident in the distribution curves for cell-specific ADAMTS-4 labelling. Cell-by-cell analysis showed that ADAMTS-4 levels were higher in chondrocytes with cytoplasmic processes compared to normal cells (P=0.044) however cells in clusters had lower levels than normal cells (P=0.003;[3(436)]). Preliminary data suggested that ADAMTS-4 levels increased with larger chondrocyte clusters.These results suggest complex heterogeneous changes to levels of cell-associated ADAMTS-4 with early cartilage degeneration – increasing in cells with processes and initially decreasing in clusters. Increased levels of ADAMTS-4 are likely to produce focal areas of matrix weakness potentially leading to early cartilage degeneration.

Cbfβ Is a Novel Modulator against Osteoarthritis by Maintaining Articular Cartilage Homeostasis through TGF-β Signaling

TGF-β signaling is a vital regulator for maintaining articular cartilage homeostasis. Runx transcription factors, downstream targets of TGF-β signaling, have been studied in the context of osteoarthritis (OA). Although Runx partner core binding factor β (Cbfβ) is known to play a pivotal role in chondrocyte and osteoblast differentiation, the role of Cbfβ in maintaining articular cartilage integrity remains obscure. This study investigated Cbfβ as a novel anabolic modulator of TGF-β signaling and determined its role in articular cartilage homeostasis. Cbfβ significantly decreased in aged mouse articular cartilage and human OA cartilage. Articular chondrocyte-specific Cbfb-deficient mice (Cbfb△ac/△ac) exhibited early cartilage degeneration at 20 weeks of age and developed OA at 12 months. Cbfb△ac/△ac mice showed enhanced OA progression under the surgically induced OA model in mice. Mechanistically, forced expression of Cbfβ rescued Type II collagen (Col2α1) and Runx1 expression in Cbfβ-deficient chondrocytes. TGF-β1-mediated Col2α1 expression failed despite the p-Smad3 activation under TGF-β1 treatment in Cbfβ-deficient chondrocytes. Cbfβ protected Runx1 from proteasomal degradation through Cbfβ/Runx1 complex formation. These results indicate that Cbfβ is a novel anabolic regulator for cartilage homeostasis, suggesting that Cbfβ could protect OA development by maintaining the integrity of the TGF-β signaling pathway in articular cartilage.

Injury-related cell death and proteoglycan loss in articular cartilage: Numerical model combining necrosis, reactive oxygen species, and inflammatory cytokines.

Osteoarthritis (OA) is a common musculoskeletal disease that leads to deterioration of articular cartilage, joint pain, and decreased quality of life. When OA develops after a joint injury, it is designated as post-traumatic OA (PTOA). The etiology of PTOA remains poorly understood, but it is known that proteoglycan (PG) loss, cell dysfunction, and cell death in cartilage are among the first signs of the disease. These processes, influenced by biomechanical and inflammatory stimuli, disturb the normal cell-regulated balance between tissue synthesis and degeneration. Previous computational mechanobiological models have not explicitly incorporated the cell-mediated degradation mechanisms triggered by an injury that eventually can lead to tissue-level compositional changes. Here, we developed a 2-D mechanobiological finite element model to predict necrosis, apoptosis following excessive production of reactive oxygen species (ROS), and inflammatory cytokine (interleukin-1)-driven apoptosis in cartilage explant. The resulting PG loss over 30 days was simulated. Biomechanically triggered PG degeneration, associated with cell necrosis, excessive ROS production, and cell apoptosis, was predicted to be localized near a lesion, while interleukin-1 diffusion-driven PG degeneration was manifested more globally. Interestingly, the model also showed proteolytic activity and PG biosynthesis closer to the levels of healthy tissue when pro-inflammatory cytokines were rapidly inhibited or cleared from the culture medium, leading to partial recovery of PG content. The numerical predictions of cell death and PG loss were supported by previous experimental findings. Furthermore, the simulated ROS and inflammation mechanisms had longer-lasting effects (over 3 days) on the PG content than localized necrosis. The mechanobiological model presented here may serve as a numerical tool for assessing early cartilage degeneration mechanisms and the efficacy of interventions to mitigate PTOA progression.

Early diagnosis and treatment of osteoarthritis with a Au@PDA-WL NP nano-probe by photoacoustic imaging.

A photoacoustic imaging (Au@PDA-WL NPs) probe was successfully prepared for monitoring the early degeneration of articular cartilage. WYRGRL immobilized on the surface of Au@PDA NPs could target the collagen II peptide, which is expressed on chondrocytes in vivo and in vitro, and the enrichment of this nano-probe on cartilage tissue further resulted in the localized plasmon resonance coupling effect, inducing an enhancement in photothermal conversion capacity after the formation of aggregates. Besides, the catechol structure in the PDA shell could eliminate ROS to effectively delay the development of osteoarthrosis.

High frame rate deformation analysis of knee cartilage by spiral dualMRI and relaxation mapping.

Daily activities including walking impose high-frequency cyclic forces on cartilage and repetitive compressive deformation. Analyzing cartilage deformation during walking would provide spatial maps of displacement and strain and enable viscoelastic characterization, which may serve as imaging biomarkers for early cartilage degeneration when the damage is still reversible. However, the time-dependent biomechanics of cartilage is not well described, and how defects in the joint impact the viscoelastic response is unclear. We used spiral acquisition with displacement-encoding MRI to quantify displacement and strain maps at a high frame rate (25 frames/s) in tibiofemoral joints. We also employed relaxometry methods (T1 , T1ρ , T2 , T2 *) on the cartilage. Normal and shear strains were concentrated on the bovine tibiofemoral contact area during loading, and the defected joint exhibited larger compressive strains. We also determined a positive correlation between the change of T1ρ in cartilage after cyclic loading and increased compressive strain on the defected joint. Viscoelastic behavior was quantified by the time-dependent displacement, where the damaged joint showed increased creep behavior compared to the intact joint. This technique was also successfully demonstrated on an in vivo human knee showing the gradual change of displacement during varus load. Our results indicate that spiral scanning with displacement encoding can quantitatively differentiate the damaged from intact joint using the strain and creep response. The viscoelastic response identified with this methodology could serve as biomarkers to detect defects in joints in vivo and facilitate the early diagnosis of joint diseases such as osteoarthritis.

Age-Dependent Changes in Knee Cartilage T1 , T2 , and T1p Simultaneously Measured Using MRI Fingerprinting.

Magnetic resonance fingerprinting (MRF) techniques have been recently described for simultaneous multiparameter cartilage mapping of the knee although investigation of their ability to detect early cartilage degeneration remains limited. To investigate age-dependent changes in knee cartilage T1 , T2 , and T1p relaxation times measured using a three-dimensional (3D) MRF sequence in healthy volunteers. Prospective. The study group consisted of 24 healthy asymptomatic human volunteers (15 males with mean age 34.9 ± 14.4 years and 9 females with mean age 44.5 ± 13.1 years). A 3.0 T gradient-echo-based 3D-MRF sequence was used to simultaneously create proton density-weighted images and T1 , T2 , and T1p maps of knee cartilage. Mean global cartilage and regional cartilage (lateral femur, lateral tibia, medial femur, medial tibia, and patella) T1 , T2 , and T1ρ relaxation times of the knee were measured. Kruskal-Wallis tests were used to compared cartilage T1 , T2 , and T1ρ relaxation times between different age groups, while Spearman correlation coefficients was used to determine the association between age and cartilage T1 , T2 , and T1ρ relaxation times. The value of P < 0.05 was considered statistically significant. Higher age groups showed higher global and regional cartilage T1 , T2 , and T1ρ . There was a significant difference between age groups in global cartilage T2 and T1ρ but no significant difference (P=0.13) in global cartilage T1. Significant difference was also present between age groups in cartilage T2 and T1ρ for medial femur cartilage and medial tibia cartilage. There were significant moderate correlations between age and T2 and T1ρ for global cartilage (R2 =0.63-0.64), medial femur cartilage (R2 =0.50-0.56), and medial tibia cartilage (R2 =0.54-0.66). Cartilage T2 and T1p relaxation times simultaneously measured using a 3D-MRF sequence in healthy volunteers showed age-dependent changes in knee cartilage, primarily within the medial compartment.

Knee Kinematic Patterns and Early Cartilage Lesion Characteristics in Patients with Anterior Cruciate Ligament Reconstruction.

Specific knee kinematic alterations have been theorized to correlate with the progression of cartilage degeneration, and therefore, post-traumatic osteoarthritis in patients with anterior cruciate ligament reconstruction (ACLR). However, how specific knee kinematic alterations contribute to knee joint cartilage degenerations remains to be unclear. To solve this problem, we hypothesized that there are specific cartilage-degenerating kinematic gait patterns that could be supported by the specific areas of cartilage lesions in ACLR knees. Thirty patients with unilateral ACLR knees and 30 healthy controls were recruited for the study. The kinematic differences between the ACLR knees and the healthy control knees during the stance phase were calculated to identify the kinematic patterns. Cartilage lesion distribution characteristics were acquired for patients with ACLR knees to validate the kinematic patterns using magnetic resonance images. Two kinematic patterns were modeled, i.e., sagittal (increased flexion angle and posterior tibial translation) and coronal (increased lateral tibial translation and abduction angle) kinematic patterns. For the sagittal pattern, the cartilage lesion distributions showed that there were more cartilage lesions (CLs) in the superoposterior regions than the posterior regions in the femoral condyles (p = 0.001), and more CLs in the posterior regions than the middle regions in the tibial plateau (p < 0.001). For the coronal pattern, the cartilage lesion distributions showed that there were more CLs in the lateral compartments near the tibial spine than the medial compartments near the tibial spine (tibial sides, p = 0.005 and femoral sides, p = 0.290). To conclude, the cartilage degeneration distribution evidence largely supports that the two kinematic patterns may contribute to cartilage degeneration in ACLR knees. These findings may provide a potential strategy of delaying early cartilage degeneration in ACLR knees by using motion (kinematic) pattern modification or training. However, investigations should be conducted on the actual effects of this potential strategy.

Dose-response relationship of in vivo ambulatory load and mechanosensitive cartilage biomarkers-The role of age, tissue health and inflammation: A study protocol.

ObjectiveTo describe a study protocol for investigating the in vivo dose-response relationship between ambulatory load magnitude and mechanosensitive blood markers of articular cartilage, the influence of age, cartilage tissue health and presence of inflammation on this relationship, and its ability to predict changes in articular cartilage quality and morphology within 2 years.DesignProspective experimental multimodal (clinical, biomechanical, biological) data collection under walking stress and three different load conditions varied in a randomized crossover design.Experimental protocolAt baseline, equal numbers of healthy and anterior cruciate ligament injured participants aged 20–30 or 40–60 years will be assessed clinically and complete questionnaires regarding their knee health. Biomechanical parameters (joint kinetics, joint kinematics, and surface electromyography) will be recorded while performing different tasks including overground and treadmill walking, single leg balance and hopping tasks. Magnetic resonance images (MRI) of both of knees will be obtained. On separate stress test days, participants will perform a 30-minute walking stress with either reduced (80% body weight (BW)), normal (100%BW) or increased (120%BW) load. Serum blood samples will be taken immediately before, immediately after, 30, 120 and 210 minutes after the walking stress. Concentration of articular cartilage blood biomarkers will be assessed using enzyme linked immunosorbent assays. At 24-month follow-up, participants will be again assessed clinically, undergo an MRI, complete questionnaires, and have a blood sample taken.ConclusionThe study design provides a standardized set up that allows to better understand the influence of ambulatory load on articular cartilage biomarkers and thereby extend current knowledge on in vivo cartilage metabolism and mechanosensitivity. Further, this study will help to elucidate the prognostic value of the load-induced cartilage biomarker response for early articular cartilage degeneration.Trial registrationThe protocol was approved by the regional ethics committee and has been registered at clinicaltrials.gov (NCT04128566).