Early Degeneration Of Articular Cartilage Research Articles

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.

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).

Preliminary study on the assessment of early cartilage degeneration by quantitative ultrashort echo time magnetic resonance imaging in vivo

To investigate the feasibility of quantitative ultrashort echo time magnetic resonance imaging (UTE-MRI) techniques for assessing early cartilage degeneration in vivo. A total of 46 patients with knee pain due to osteoarthritis (OA) as the main complaint were recruited into the study. We performed MRI examinations with different quantitative UTE-MRI techniques, including UTE-based magnetization transfer (MT), UTE-adiabaticT1ρ, and UTE-T2* mapping on a 3.0T clinical magnetic resonance (MR) scanner (MR750; GE Healthcare, Milwaukee, WI, USA). Three regions of interest (ROIs) were manually drawn on the medial and lateral femoral condyles and the corresponding medial and lateral tibial plateaus, respectively. A total of 561 ROIs (12 ROIs for each knee) were finally included and divided into 3 groups according to the MRI Osteoarthritis Knee Score (MOAKS): normal (MOAKS 0, n=175), mild degeneration (MOAKS 1, n=283), and moderate degeneration (MOAKS 2, n=103). One-way analysis of variance (ANOVA) and Tamhane's T2 test were used to compare the differences of quantitative UTE-biomarkers among different groups. The analysis of Spearman's correlation was used to assess the correlation between the UTE-biomarkers and MOAKS grading. The diagnostic efficacy of different quantitative UTE-MRI techniques for detecting mild cartilage degeneration was evaluated using the receiver operating characteristic (ROC) curve. The UTE-MT ratio (UTE-MTR) and the UTE-adiabatic T1ρ values had a moderate correlation with the MOAKS grading (r=-0.523, P<0.001; r=0.531, P<0.001, respectively), while the UTE-T2* was weakly correlated with the MOAKS grading (r=-0.396, P<0.001). For the normal group (MOAKS 0) and the mild group (MOAKS 1), the UTE-MTR values were 21.09%±3.03% and 17.30%±3.22%, respectively. The UTE-adiabatic T1ρ values were 30.43±6.26 ms and 35.05±8.78 ms for the normal group (MOAKS 0) and the mild group (MOAKS 1), respectively. With respect to the UTE-T2* values, the normal group (MOAKS 0) values were 21.49±3.96 ms and the mild group (MOAKS 1) values were 19.86±3.08 ms. All the differences between the 2 groups of the 3 UTE-MRI values were significant. The AUCs of the UTE-MTR, UTE-adiabatic T1ρ, and UTE-T2* mapping were 0.794, 0.732, and 0.651, respectively. The quantitative UTE-MRI techniques (UTE-MT, UTE-adiabatic T1ρ, and UTE-T2* mapping) show great promise for assessing the early degeneration of articular cartilage in vivo, and the UTE-MT and UTE-adiabatic T1ρ values show better diagnostic efficacy than UTE-T2* mapping.

T1ρ magnetic resonance imaging for quantitative assessment of patella cartilage in healthy subjects and athletes

Knee osteoarthritis (OA) is one of major reasons to causes pain and limit mobility for aging people. Early diagnosis of articular cartilage degeneration is of utmost importance for the prevention of OA. Thus, it is necessary to develop a novel magnetic resonance imaging technique to detect the early articular cartilage degeneration. Methods. T1ρ and T2-weighted images of the knees were obtained for 50 asymptomatic young subjects (23 men and 27 women; average age, 23.9 ± 1.8 years) and 17 Chinese National Men's hockey players (average age, 20.7 ± 1.1 years), using a 3.0-T MRI scanner. Quantitative T1ρ relaxation maps of the bilateral patella cartilage were generated by post-processing, and each map was divided into 15 regions of interest (ROIs). T1ρ values of each ROI were measured and compared between asymptomatic subjects and athletes. Results. T1ρ values of left patellar cartilage in athletes were significantly higher than those in healthy subjects (P < 0.05). T1ρ values of right patellar cartilage in athletes were also higher than healthy controls (P < 0.05). T1ρ values of patellar cartilage in both athletes and healthy subjects uncovered no apparent difference between the left knees and right knees (P > 0.05). Conclusion. T1ρ MRI could potentially represent a useful tool for the measurement of early articular cartilage degeneration in clinical practice.

Early patellofemoral articular cartilage degeneration in a rat model of patellar instability is associated with activation of the NF-\u03baB signaling pathway

BackgroundPatellar instability (PI) often increases the possibility of lateral patellar dislocation and early osteoarthritis. The molecular mechanism of early articular cartilage degeneration during patellofemoral osteoarthritis (PFOA) still requires further investigation. However, it is known that the NF-κB signaling pathway plays an important role in articular cartilage degeneration. The aim of this study was to investigate the relationship between the NF-κB signaling pathway and patellofemoral joint cartilage degeneration.MethodsWe established a rat model of PI-induced PFOA. Female 4-week-old Sprague-Dawley rats (n = 120) were randomly divided into two groups: the PI (n = 60) and control group (n = 60). The distal femurs of the PI and control group were isolated and compared 4, 8, and 12 weeks after surgery. The morphological structure of the trochlear cartilage and subchondral bone were evaluated by micro-computed tomography and histology. The expression of NF-κB, matrix metalloproteinase (MMP)-13, collagen X, and TNF-ɑ were evaluated by immunohistochemistry and quantitative polymerase chain reaction.ResultsIn the PI group, subchondral bone loss and cartilage degeneration were found 4 weeks after surgery. Compared with the control group, the protein and mRNA expression of NF-κB and TNF-ɑ were significantly increased 4, 8, and 12 weeks after surgery in the PI group. In addition, the markers of cartilage degeneration MMP-13 and collagen X were more highly expressed in the PI group compared with the control group at different time points after surgery.ConclusionsThis study has demonstrated that early patellofemoral joint cartilage degeneration can be caused by PI in growing rats, accompanied by significant subchondral bone loss and cartilage degeneration. In addition, the degeneration of articular cartilage may be associated with the activation of the NF-κB signaling pathway and can deteriorate with time as a result of PI.

Relationship of alignment in the lower extremity with early degeneration of articular cartilage after resection of the medial meniscus: Quantitative analysis using T2 mapping.

The objective of this study was to examine the relationship between cartilage degeneration early after partial medial meniscectomy and abnormal alignment in the lower extremity.The subjects were 34 patients (37 knees) with medial meniscal tear who underwent arthroscopic partial meniscectomy. MRI was performed before and 6 months after surgery. T2 mapping images in sagittal sections of medial femoral condyle were produced and 10 regions of interest were set at intervals of 10° in the articular cartilage in the femur. Subjects with an increase in T2 of ≥6% at a flexion angle of 30° were assigned to the degeneration group. Patient background, hip-knee-ankle (HKA) angle, and total resection of meniscal segments were compared between this group and the other patients to identify factors involved in degeneration of articular cartilage.T2 values 6 months after surgery in 3 ROIs at flexion angles of 30° to 50° were significantly longer than those before surgery. The preoperative HKA angle was significantly higher in the degeneration group. T2 values in articular cartilage of the femoral condyle increased earlier after meniscectomy with abnormal alignment in the lower extremity.Meniscectomy in cases with abnormal alignment may have a risk of early onset of osteoarthritis.Level of evidence: Level IV

HMGB2 is a novel adipogenic factor that regulates ectopic fat infiltration in skeletal muscles

Although various surgical procedures have been developed for chronic rotator cuff tear repair, the re-tear rate remains high with severe fat infiltration. However, little is known about the molecular regulation of this process. Mesenchymal stem cells (MSCs) in the intra-muscular space are origin of ectopic fat cells in skeletal muscle. We have previously shown that high-mobility group box 2 (HMGB2), which is a nuclear protein commonly associated with mesenchymal differentiation, is involved in the early articular cartilage degeneration. In this study, we addressed the role of HMGB2 in adipogenesis of MSCs and fat infiltration into skeletal muscles. HMGB2 was highly expressed in undifferentiated MSCs and co-localized with platelet-derived growth factor receptor α (PDGFRA) known as an MSC-specific marker, while their expressions were decreased during adipocytic differentiation. Under the deficiency of HMGB2, the expressions of adipogenesis-related molecules were reduced, and adipogenic differentiation is substantially impaired in MSCs. Moreover, HMGB2+ cells were generated in the muscle belly of rat supraspinatus muscles after rotator cuff transection, and some of these cells expressed PDGFRA in intra-muscular spaces. Thus, our findings suggest that the enhance expression of HMGB2 induces the adipogenesis of MSCs and the fat infiltration into skeletal muscles through the cascade of HMGB2-PDGFRA.

Electromechanical probe and automated indentation maps are sensitive techniques in assessing early degenerated human articular cartilage.

Recent advances in the development of new drugs to halt or even reverse the progression of Osteoarthritis at an early-stage requires new tools to detect early degeneration of articular cartilage. We investigated the ability of an electromechanical probe and an automated indentation technique to characterize entire human articular surfaces for rapid non-destructive discrimination between early degenerated and healthy articular cartilage. Human cadaveric asymptomatic articular surfaces (four pairs of distal femurs and four pairs of tibial plateaus) were used. They were assessed ex vivo: macroscopically, electromechanically, (maps of the electromechanical quantitative parameter, QP, reflecting streaming potentials), mechanically (maps of the instantaneous modulus, IM), and through cartilage thickness. Osteochondral cores were also harvested from healthy and degenerated regions for histological assessment, biochemical analyses, and unconfined compression tests. The macroscopic visual assessment delimited three distinct regions on each articular surface: Region I was macroscopically degenerated, region II was macroscopically normal but adjacent to regions I and III was the remaining normal articular surface. Thus, each extracted core was assigned to one of the three regions. A mixed effect model revealed that only the QP (p < 0.0001) and IM (p < 0.0001) were able to statistically discriminate the three regions. Effect size was higher for QP and IM than other assessments, indicating greater sensitivity to distinguish early degeneration of cartilage. When considering the mapping feature of the QP and IM techniques, it also revealed bilateral symmetry in a moderately similar distribution pattern between bilateral joints. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:858-867, 2017.

Effects of resveratrol on collagen type II protein in the superficial and middle zone chondrocytes of porcine articular cartilage

Ethnopharmacological relevanceResveratrol (RSV) was first isolated in 1940 from the roots of white hellebore (Veratrum grandiflorum (Maxim. ex Miq) O. Loes) and in 1963 from the roots of Japanese knotweed (Polygonum cuspidatum Siebold & Zucc.). These species have been used traditionally to treat arthritis, gout or inflammation. RSV (3,5,4-trihydroxystilbene) is a polyphenolic phytoalexin compound found in various plants, such as grape vines, berries, peanuts, seeds and roots; the highest concentration is in the skin of red grapes. This component of red wine has potent anti-inflammatory properties and may reduce the side effects of non-steroidal anti-inflammatory drugs that are currently used for pain amelioration in osteoarthritis (OA). In early degeneration of articular cartilage, which may lead to OA there is a loss of the tensile properties, indicative of damage to the fibrillar network. Damage to this fibrillar meshwork, made up of primarily collagen type II (90–95%), may be a critical event in the pathology of many arthritides, due in part to the very slow rate of collagen turnover within the cartilage. Collagen type II is the pre-dominant protein of the cartilage middle zone matrix mainly responsible for tensile strength of articular cartilage. The aim of the study was to investigate the effects of RSV on the expression of collagen type II from the superficial and middle zone chondrocytes of porcine articular cartilage. Materials and methodsPorcine articular chondrocytes were isolated from the superficial and middle zone of articular cartilage, cultured as monolayers in serum-free chemically defined medium for four days. Effects of RSV on porcine articular chondrocytes were studied by assessing expression of collagen type II mRNA by RT-PCR and protein levels of collagen type II by ELISA; as well as localisation of collagen type II on cartilage tissue sections using immunohistochemistry. ResultsRSV significantly stimulated the expression of collagen type II at the mRNA and protein levels in the superficial and middle zone. Immunohistochemistry revealed that collagen type II was present along the whole cartilage tissue sections. The staining was strong in the superficial zone, mild in the middle zone and less around hypertrophic chondrocytes in the deep zone. Histological analysis confirmed that cartilage slices were obtained from specific articular cartilage zones. ConclusionThis study revealed the importance of RSV in the regulation of collagen type II protein in different zones of articular cartilage.

T1ρ magnetic resonance imaging quantification of early articular cartilage degeneration in a rabbit model.

BackgroundOsteoarthritis (OA) is a serious problem in the recent aging society, and early diagnosis and intervention of articular cartilage degeneration are very important for the onset of OA. Therefore, development of newer MRI techniques is necessary and expected for detection of early articular cartilage degeneration.Methods24 rabbits were randomly divided into four equal experimental groups (Group A, B, C, D) to establish articular cartilage models in different grades of early degeneration by injecting papain into the left knee joint cavity. Another 8 rabbits were considered as blank control (Group E), and then randomized into four subgroups (EA, EB, EC, ED). T1ρ and T2-weighted images of the bilateral knee joints were obtained for rabbits by using 3.0 T MRI. Group A, B, C, and D were imaged respectively at 1, 2, 3, and 4 weeks post-operation, and EA, EB, EC, ED underwent the same period imaging. Rabbits were sacrificed after scanning and the femoral condyle cartilage (FCC) was histological examined. T1ρ values of the femoral condyle cartilage were measured and statistically analyzed, and contrasted with the histologic results.ResultsT1ρ values of the left side in experimental groups were significantly higher than the right side (P < 0.05), and which increased gradually with the passage of post-operation time (P < 0.05). Histological examination demonstrated the proteoglycan content of the left side decreased, and indicated the occurrence of early degeneration.ConclusionsT1ρ MRI can sensitively and quantitatively reflect the change in proteoglycans prior to the morphologic alterations of articular cartilage, and T1ρ value is gradually increased with a decrease in proteoglycan content, therefore that T1ρ could potentially act as a reliable tool to identify early cartilage degeneration.

T2 and T2* Mapping

New noninvasive biochemical quantitative magnetic resonance imaging (MRI) techniques are increasingly applied in cartilage repair and osteoarthritis (OA), where quantitative T2 mapping and initially also T2* mapping are seen as valid biomarkers. These quantitative MR biomarkers detect early degeneration of articular cartilage, mainly represented by increasing water content and a disruption of the collagen network. Recently, feasibility of biochemical MR imaging of repair tissue and the surrounding cartilage after cartilage repair procedures has been demonstrated. Different ultrastructural properties of the repair tissue after different repair procedures, such as microfracturing and autologous chondrocyte implantation, resulted in differences in imaging characteristics. Further, these biochemical imaging characteristics varied during follow-up and are able to depict repair tissue maturation. Within these approaches, zonal stratification analysis was considered crucial. Comparably in OA, T2 mapping seems to provide additional information during different stages of cartilage degeneration and can be used in patient subgroups as a predictor for disease progression. Although the results in various studies employing T2 and T2* mapping are very promising and valuable additional information on cartilage ultrastructure can be obtained, (comparable to all the other quantitative cartilage imaging techniques) further multimodal investigation is needed especially since a standard of reference is hard to define.

An Ultrasound Biomicroscopic and Water Jet Ultrasound Indentation Method for Detecting the Degenerative Changes of Articular Cartilage in a Rabbit Model of Progressive Osteoarthritis

It is important to assess the early degeneration of articular cartilage associated with osteoarthritis (OA) for early intervention and treatment planning. Previously, we have developed a high frequency ultrasound and water jet indentation method for the morphologic, acoustic and mechanical assessment of articular cartilage, using the enzymatic digestion as a model of osteoarthritic degeneration. No naturally degenerated articular cartilage has been tested with the developed method. In this study, we aimed to determine the usefulness of the developed method for detecting the natural degeneration of articular cartilage in a standard surgical model of OA in rabbits. Forty adult New Zealand white female rabbits were used in this study, which included 30 experimental rabbits undergoing the right anterior cruciate ligament transection surgery and 10 control rabbits. At the 3rd, 6th, and 9th week post-surgery, 10 experimental rabbits were sacrificed, respectively, for assessment of the knee cartilage quality. The cartilage at the medial and lateral femoral condyles and tibial plateaus (four points) was measured by the high frequency ultrasound biomicroscopy, the water jet ultrasound indentation and a contact mechanical indentation test before a histopathologic analysis for grading of degeneration severity. Measured parameters were compared among different groups classified either by post-surgery time or by histopathologic grade. The results showed a general trend of increase for ultrasound roughness index and a general trend of decrease for integrated reflection coefficient, stiffness coefficient from water-jet indentation and Young's modulus (E) from the mechanical indentation with the increase of post-surgery time. Comparisons among groups with different histopathologic grades showed similar trend with the increase of degeneration severity. The water jet ultrasound indentation method was demonstrated to be an effective method to measure the mechanical properties of the articular cartilage and with further development of arthroscopic ultrasound probe; it has the ability to assess the early degeneration of articular cartilage with measurement of morphologic, acoustic and mechanical properties of the cartilage in vivo.

Cartilage repair surgery: outcome evaluation by using noninvasive cartilage biomarkers based on quantitative MRI techniques?

Background. New quantitative magnetic resonance imaging (MRI) techniques are increasingly applied as outcome measures after cartilage repair. Objective. To review the current literature on the use of quantitative MRI biomarkers for evaluation of cartilage repair at the knee and ankle. Methods. Using PubMed literature research, studies on biochemical, quantitative MR imaging of cartilage repair were identified and reviewed. Results. Quantitative MR biomarkers detect early degeneration of articular cartilage, mainly represented by an increasing water content, collagen disruption, and proteoglycan loss. Recently, feasibility of biochemical MR imaging of cartilage repair tissue and surrounding cartilage was demonstrated. Ultrastructural properties of the tissue after different repair procedures resulted in differences in imaging characteristics. T2 mapping, T1rho mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), and diffusion weighted imaging (DWI) are applicable on most clinical 1.5 T and 3 T MR scanners. Currently, a standard of reference is difficult to define and knowledge is limited concerning correlation of clinical and MR findings. The lack of histological correlations complicates the identification of the exact tissue composition. Conclusions. A multimodal approach combining several quantitative MRI techniques in addition to morphological and clinical evaluation might be promising. Further investigations are required to demonstrate the potential for outcome evaluation after cartilage repair.

Physiological assessment of in vivo human knee articular cartilage using sodium MR imaging at 1.5 T

Osteoarthritis is a common joint disorder that is most prevalent in the knee joint. Knee osteoarthritis (OA) can be characterized by the gradual loss of articular cartilage (AC). Formation of lesion, fissures and cracks on the cartilage surface has been associated with degenerative AC and can be measured by morphological assessment. In addition, loss of proteoglycan from extracellular matrix of the AC can be measured at early stage of cartilage degradation by physiological assessment. In this case, a biochemical phenomenon of cartilage is used to assess the changes at early degeneration of AC. In this paper, a method to measure local sodium concentration in AC due to proteoglycan has been investigated. A clinical 1.5-T magnetic resonance imaging (MRI) with multinuclear spectroscopic facility is used to acquire sodium images and quantify local sodium content of AC. An optimised 3D gradient-echo sequence with low echo time has been used for MR scan. The estimated sodium concentration in AC region from four different data sets is found to be ~225±19mmol/l, which matches the values that has been reported for the normal AC. This study shows that sodium images acquired at clinical 1.5-T MRI system can generate an adequate quantitative data that enable the estimation of sodium concentration in AC. We conclude that this method is potentially suitable for non-invasive physiological (sodium content) measurement of articular cartilage.

Effect of Combined Traumatic Impact and Radial Transection of Medial Meniscus on Knee Articular Cartilage in a Rabbit In Vivo Model

The purpose of this study was to test the hypothesis that combined meniscectomy and traumatic impact accelerate early degeneration of articular cartilage in the knee versus meniscectomy alone. A previously published in vivo rabbit cartilage impact model was used combined with radial transection of the medial meniscus posterior horn versus meniscal transection alone. Rabbits were killed 3 months after surgery. Quantitative histologic analysis of the articular cartilage proteoglycan depth and glycosaminoglycan (GAG) fraction was performed at the site of impact on the posterior femoral condyle (PFC) and at the distal femoral condyle (DFC) overlying the meniscectomy in the surgical knee and the contralateral control knee. The articular cartilage in the knees that underwent isolated meniscectomy did not differ significantly from the contralateral control knees for any measured value. The knees with a combined insult had a lower GAG fraction (P = .03) at the PFC and a greater depth of proteoglycan loss at both the PFC (P = .02) and the DFC (P = .04) versus contralateral controls. Compared with meniscectomy alone, the combined-insult knees had a greater depth of proteoglycan loss at the DFC (P = .005). On the basis of early results using GAG fraction and proteoglycan depth, combined traumatic impact and meniscectomy are more damaging to articular cartilage than meniscectomy alone. A knee with a combination of meniscal injury and articular cartilage impact may be at particularly high risk for early joint degeneration.

Serum CTXii Correlates With Articular Cartilage Degeneration After Anterior Cruciate Ligament Transection or Arthrotomy Followed by Standardized Exercise

Background:Anterior cruciate ligament injury increases risk for accelerated development of osteoarthritis. The effect of exercise on articular cartilage following joint injury is not well understood. Biochemical biomarkers of collagen degradation and proteoglycan turnover are potential indicators for early articular cartilage degeneration.Hypothesis:This study tests the hypothesis that serum concentrations of CS846 and CTXii correlate with structural changes to articular cartilage following joint injury in exercised animals.Study Design:Controlled laboratory study.Methods:Twenty-four Sprague-Dawley rats underwent either arthrotomy alone (sham surgery) or anterior cruciate ligament transection (ACLT). Animals were recovered for 3 weeks and then exercised on a treadmill at 18 m per minute, 1 hour per day, 5 days per week, until sacrifice either 6 or 12 weeks later. Articular cartilage was assessed grossly, and histology was graded using modified Mankin, toluidine blue, and modified David-Vaudey scales. Serum collected preoperatively and at sacrifice was assayed by ELISA for CTXii and CS846.Results:At 6 weeks, gross grades (P < 0.01), modified Mankin scores (P < 0.03), and toluidine blue scores (P < 0.04) were higher, reflecting increased degeneration in ACLT animals compared with sham surgery animals. Serum CS846 increased after 6 weeks in ACLT animals (P < 0.05). Serum CTXii levels strongly correlated with Mankin degenerative scores (coefficient = 0.81, P < 0.01) and David-Vaudey histology grades (coefficient = 0.73, P < 0.01) at 6 weeks. While gross grades remained higher at 12 weeks in ACLT animals (P < 0.04), no differences were seen in serum CS846 and CTXii. Histology scores also showed no differences between ACLT and sham due to increasing degeneration in the sham surgery group.Conclusion:The strong correlation between serum CTXii and microstructural changes to articular cartilage following joint injury demonstrates potential use of serum biomarkers for early detection of cartilage degeneration. Increasing cartilage degeneration in exercised sham-surgery animals suggests that early loading may have negative effects on articular cartilage due to either mechanical injury or hemarthrosis after arthrotomy.Clinical Relevance:Patients with anterior cruciate ligament injury are at increased risk for development of posttraumatic osteoarthritis. CTXii may be useful for early detection of joint degeneration. Further study on the effects of exercise after injury is important to postinjury and postoperative rehabilitation.

In-situ imaging of articular cartilage of the first carpometacarpal joint using co-registered optical coherence tomography and computed tomography

Conventional imaging modalities are unable to depict the early degeneration of articular cartilage in osteoarthritis, especially in small joints. Optical coherence tomography has previously been used successfully in high-resolution imaging of cartilage tissue. This pilot cadaver study demonstrates the use of intra-articular optical coherence tomography in imaging of articular cartilage of the first carpometacarpal joint, producing high resolution images of the articular surface in which cartilage thickness and surface characteristics were assessed. Findings on optical coherence tomography were confirmed with histology. Furthermore, co-registration of optical coherence tomography and computed tomography was used to accurately determine the scanned trajectory and reconstruct a true-scale image overlay.

Quantitative Imaging of Young’s Modulus of Soft Tissues from Ultrasound Water Jet Indentation: A Finite Element Study

Indentation testing is a widely used approach to evaluate mechanical characteristics of soft tissues quantitatively. Young's modulus of soft tissue can be calculated from the force-deformation data with known tissue thickness and Poisson's ratio using Hayes' equation. Our group previously developed a noncontact indentation system using a water jet as a soft indenter as well as the coupling medium for the propagation of high-frequency ultrasound. The novel system has shown its ability to detect the early degeneration of articular cartilage. However, there is still lack of a quantitative method to extract the intrinsic mechanical properties of soft tissue from water jet indentation. The purpose of this study is to investigate the relationship between the loading-unloading curves and the mechanical properties of soft tissues to provide an imaging technique of tissue mechanical properties. A 3D finite element model of water jet indentation was developed with consideration of finite deformation effect. An improved Hayes' equation has been derived by introducing a new scaling factor which is dependent on Poisson's ratios v, aspect ratio a/h (the radius of the indenter/the thickness of the test tissue), and deformation ratio d/h. With this model, the Young's modulus of soft tissue can be quantitatively evaluated and imaged with the error no more than 2%.

Ultrasound speed and attenuation in progressive trypsin digested articular cartilage

Subtle changes of articular cartilage (AC) can lead to tissue degeneration and even osteoarthritis (OA). The early degeneration of AC is closely related to a change in proteoglycans (PG) content. The observation of PG is therefore an appropriate way of studying OA and evaluating the degree of AC degeneration. In this study, 20 cartilage-bone samples were prepared from normal porcine femoral condyle cartilage and 10 samples were digested over 2 h using 0.25% trypsin solution. The dynamic process of PG-digestion was explored using a conventional A-mode ultrasound (US) experimental system with a 10 MHz center frequency. Quantitative acoustic parameters were calculated from ultrasonic radio-frequency echo signals and included US speed (USS), US amplitude attenuation coefficient (UAA) and broadband US attenuation coefficient (BUA). The experimental results showed that the conventional A-mode ultrasound is valuable for tracking the degree of PG-digestion. Histology also confirmed the validity of the ultrasound observations. For every AC sample, the degree of PG-digestion within a given time was different and was affected by individual differences. After two hours of degeneration, USS showed a mean decrease of 0.4% (P<0.05). UAA was significantly lower after a two-hour PG depletion period (from (2.45±0.23) to (2.28±0.41) dB mm⁻¹). BUA showed no significant differences during this process. In conclusion, conventional ultrasound can provide useful information about trypsin-induced progressive PG depletion in AC and can reflect variations of PG content via the quantitative acoustic parameters USS and UAA. The results of this study may be used to identify an indirect indicator of cartilage matrix integrity and OA disease progression.

Joint Inflammation and Early Degeneration Induced by High‐Force Reaching Are Attenuated by Ibuprofen in an Animal Model of Work‐Related Musculoskeletal Disorder

We used our voluntary rat model of reaching and grasping to study the effect of performing a high-repetition and high-force (HRHF) task for 12 weeks on wrist joints. We also studied the effectiveness of ibuprofen, administered in the last 8 weeks, in attenuating HRHF-induced changes in these joints. With HRHF task performance, ED1+ and COX2+ cells were present in subchondral radius, carpal bones and synovium; IL-1alpha and TNF-alpha increased in distal radius/ulna/carpal bones; chondrocytes stained with Terminal deoxynucleotidyl Transferase- (TDT-) mediated dUTP-biotin nick end-labeling (TUNEL) increased in wrist articular cartilages; superficial structural changes (e.g., pannus) and reduced proteoglycan staining were observed in wrist articular cartilages. These changes were not present in normal controls or ibuprofen treated rats, although IL-1alpha was increased in reach limbs of trained controls. HRHF-induced increases in serum C1,2C (a biomarker of collagen I and II degradation), and the ratio of collagen degradation to synthesis (C1,2C/CPII; the latter a biomarker of collage type II synthesis) were also attenuated by ibuprofen. Thus, ibuprofen treatment was effective in attenuating HRHF-induced inflammation and early articular cartilage degeneration.