scholarly journals Comparison of properties determined using electromechanical assessment (Arthro-BST™) with macroscopic and histological properties in symptomatic human articular cartilage of the hip

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Taku Ukai ◽  
Masato Sato ◽  
Shiho Wasai ◽  
Takumi Takahashi ◽  
Haruka Omura ◽  
...  
Keyword(s):  
Histological Grade ◽  
Cartilage Damage ◽  
Hip Osteoarthritis ◽  
Cartilage Degeneration ◽  
Research Society ◽  
Cartilage Tissue ◽  
Human Articular Cartilage ◽  
Mankin Score ◽  
Osteoarthritis Research Society ◽  
Noninvasive Assessment

Abstract Background Cartilage degeneration is assessed using various methods. Although macroscopic evaluation can directly measure cartilage degeneration, it cannot accurately assess cartilage properties. Histological examination is one of the most accurate methods for evaluating cartilage degeneration. However, it is invasive and requires collection of cartilage tissue. In contrast, the Arthro-BST™ probe can assess cartilage properties noninvasively. This study aimed to evaluate the effectiveness of the Arthro-BST in assessing cartilage degeneration by comparing macroscopic (International Cartilage Repair Society [ICRS] classification) and histological evaluations (modified Mankin score and Osteoarthritis Research Society International [OARSI] histological grade). Methods Fourteen femoral heads were excised from 13 patients during surgery to treat hip osteoarthritis or femoral fracture. The ICRS score was used for macroscopic evaluation of cartilage degeneration. The Arthro-BST was applied at sites matching the areas of cartilage damage. The sites assessed using the ICRS classification and Arthro-BST were evaluated histologically (modified Mankin score and OARSI histological grade), and these were compared with the Arthro-BST results. Results The ICRS classification identified significant differences between grades 1 and 3 (p < 0.01), between grades 1 and 4 (p < 0.01), between grades 2 and 3 (p < 0.01), and between grades 2 and 4 (p < 0.01). Significant correlations were observed between the Arthro-BST results and the ICRS score, modified Mankin score (structure, cellularity, matrix staining, total score), and OARSI histological grade. Conclusions In the assessment of hip osteoarthritis, the Arthro-BST results correlated with those of macroscopic and histological evaluations. The Arthro-BST is useful for assessing hip osteoarthritis and may be helpful for noninvasive assessment of cartilage degeneration.

Comparison of Properties Determined Using Electromechanical Assessment (Arthro-BSTTM) With Macroscopic and Histological Properties in Symptomatic Human Articular Cartilage of the Hip

2021 ◽  
Author(s):  
Taku Ukai ◽  
Masato Sato ◽  
Shiho Wasai ◽  
Takumi Takahashi ◽  
Haruka Omura ◽  
...  
Keyword(s):  
Histological Grade ◽  
Cartilage Damage ◽  
Hip Osteoarthritis ◽  
Cartilage Degeneration ◽  
Research Society ◽  
Cartilage Tissue ◽  
Histological Evaluation ◽  
Human Articular Cartilage ◽  
Mankin Score ◽  
Osteoarthritis Research Society

Abstract Background: Cartilage degeneration is assessed using various methods. Although macroscopic evaluation can measure cartilage degeneration directly, it cannot accurately assess cartilage properties. Histological examination is one of the most accurate methods for evaluating cartilage degeneration. However, it is invasive and requires collection of cartilage tissue. By contrast, the Arthro-BSTTM probe can assess cartilage properties noninvasively. This study aimed to evaluate the effectiveness of the Arthro-BST for assessing cartilage degeneration by comparing macroscopic evaluation (International Cartilage Repair Society [ICRS] classification) and histological evaluation (modified Mankin score and Osteoarthritis Research Society International [OARSI] histological grade).Methods: Fourteen femoral heads were excised from 13 patients during surgery to treat hip osteoarthritis or femoral fracture. The ICRS score was used for macroscopic evaluation of cartilage degeneration. The Arthro-BST was applied at sites matching the areas of cartilage damage. The sites assessed using the ICRS classification and Arthro-BST were evaluated histologically (modified Mankin score and OARSI histological grade), and these were compared with the Arthro-BST results.Results: ICRS classification identified significant differences between grades 1 and 3 (p < 0.01), grades 1 and 4 (p < 0.01), grades 2 and 3 (p < 0.01), and grades 2 and 4 (p < 0.01). Significant correlations were observed between the Arthro-BST results and the ICRS score, modified Mankin score (structure, cellularity, matrix staining, total score), and OARSI histological grade.Conclusions: In the assessment of hip osteoarthritis, Arthro-BST results correlated with those of macroscopic and histological evaluation. The Arthro-BST is useful for assessing hip osteoarthritis and may be helpful for the noninvasive assessment of cartilage degeneration.

scholarly journals Metformin limits osteoarthritis development and progression through activation of AMPK signalling

2020 ◽  
Vol 79 (5) ◽  
pp. 635-645 ◽  
Author(s):  
Jun Li ◽  
Bin Zhang ◽  
Wei-Xiao Liu ◽  
Ke Lu ◽  
Haobo Pan ◽  
...  
Keyword(s):  
Cartilage Degeneration ◽  
Cartilage Degradation ◽  
Research Society ◽  
Cartilage Tissue ◽  
Protective Effects ◽  
Joint Injury ◽  
Synovial Hyperplasia ◽  
Medial Meniscectomy ◽  
Osteoarthritis Research Society ◽  
Amp Activated Protein Kinase

ObjectivesIn this study, we aim to determine the effect of metformin on osteoarthritis (OA) development and progression.MethodsDestabilisation of the medial meniscus (DMM) surgery was performed in 10-week-old wild type and AMP-activated protein kinase (AMPK)α1 knockout (KO) mice. Metformin (4 mg/day in drinking water) was given, commencing either 2 weeks before or 2 weeks after DMM surgery. Mice were sacrificed 6 and 12 weeks after DMM surgery. OA phenotype was analysed by micro-computerised tomography (μCT), histology and pain-related behaviour tests. AMPKα1 (catalytic alpha subunit of AMPK) expression was examined by immunohistochemistry and immunofluorescence analyses. The OA phenotype was also determined by μCT and MRI in non-human primates.ResultsMetformin upregulated phosphorylated and total AMPK expression in articular cartilage tissue. Mild and more severe cartilage degeneration was observed at 6 and 12 weeks after DMM surgery, evidenced by markedly increased Osteoarthritis Research Society International scores, as well as reduced cartilage areas. The administration of metformin, commencing either before or after DMM surgery, caused significant reduction in cartilage degradation. Prominent synovial hyperplasia and osteophyte formation were observed at both 6 and 12 weeks after DMM surgery; these were significantly inhibited by treatment with metformin either before or after DMM surgery. The protective effects of metformin on OA development were not observed in AMPKα1 KO mice, suggesting that the chondroprotective effect of metformin is mediated by AMPK signalling. In addition, we demonstrated that treatment with metformin could also protect from OA progression in a partial medial meniscectomy animal model in non-human primates.ConclusionsThe present study suggests that metformin, administered shortly after joint injury, can limit OA development and progression in injury-induced OA animal models.

scholarly journals eNAMPT Is Localised to Areas of Cartilage Damage in Patients with Hip Osteoarthritis and Promotes Cartilage Catabolism and Inflammation

2021 ◽  
Vol 22 (13) ◽  
pp. 6719
Author(s):  
Ashleigh M. Philp ◽  
Sam Butterworth ◽  
Edward T. Davis ◽  
Simon W. Jones
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Cytokines ◽  
Cartilage Damage ◽  
Hip Osteoarthritis ◽  
Matrix Metalloproteases ◽  
Cartilage Explants ◽  
Cartilage Tissue ◽  
Human Articular Cartilage ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Pro Inflammatory Cytokines

Obesity increases the risk of hip osteoarthritis (OA). Recent studies have shown that adipokine extracellular nicotinamide phosphoribosyltransferase (eNAMPT or visfatin) induces the production of IL-6 and matrix metalloproteases (MMPs) in chondrocytes, suggesting it may promote articular cartilage degradation. However, neither the functional effects of extracellular visfatin on human articular cartilage tissue, nor its expression in the joint of hip OA patients of varying BMI, have been reported. Hip OA joint tissues were collected from patients undergoing joint replacement surgery. Cartilage explants were stimulated with recombinant human visfatin. Pro-inflammatory cytokines and MMPs were measured by ELISA and Luminex. Localisation of visfatin expression in cartilage tissue was determined by immunohistochemistry. Cartilage matrix degradation was determined by quantifying proteoglycan release. Expression of visfatin was elevated in the synovial tissue of hip OA patients who were obese, and was co-localised with MMP-13 in areas of cartilage damage. Visfatin promoted the degradation of hip OA cartilage proteoglycan and induced the production of pro-inflammatory cytokines (IL-6, MCP-1, CCL20, and CCL4) and MMPs. The elevated expression of visfatin in the obese hip OA joint, and its functional effects on hip cartilage tissue, suggests it plays a central role in the loss of cartilage integrity in obese patients with hip OA.

scholarly journals Biological Properties and Pathological Stages of Chondrocyte Colony-like Clusters in Osteoarthritic Cartilage Tissue

2020 ◽  
Author(s):  
XIAOJIAN WANG ◽  
Lei Wei ◽  
Xiaochun Wei ◽  
Yan Xue ◽  
Changqi Sun ◽  
...  
Keyword(s):  
Cartilage Degeneration ◽  
Research Society ◽  
Biological Properties ◽  
Cartilage Tissue ◽  
Osteoarthritic Cartilage ◽  
Human Knee ◽  
Osteoarthritis Research Society ◽  
Grade 3 ◽  
Pathological Stages ◽  
Hypertrophic Changes

Abstract Objective:In these studies,we investigated the timing and location of chondrocyte colony-like clusters in cartilage tissue during the development of human knee osteoarthritis(OA),and explored the biological properties of chondrocytes in colony-like clusters and their significance for degenerative cartilage tissue.Methods:Osteoarthritis Research Society International (OARSI) grade 0～6 cartilage tissue was obtained from the human tibial plateau, and histologicalsections were made to observe whether there were chondrocyte colony-like clusters in the cartilage tissue and where they occurred. Immunohistochemistry, PCR and western blotting were used to detect the biological properties of chondrocytes in the colony-like clusters and to describe the histopathological stages of the colony-like clusters according to the properties of thechondrocytes in the cluster.Results: There were a large number of chondrocyte colony-like clusters in the middle zone of OARSI grade 3 and grade 4 cartilage tissue.The chondrocytes in the colony-like clusters rapidly proliferated from one to a certain number and then rapidly underwent hypertrophic changes,synthesizing and releasing the MMP-13 protein to degrade cartilage tissue and enlarge chondrocyte lacunae.Eventually, the chondrocytes in the colony-like cluster underwent apoptosis and disappeared, leaving large empty chondrocyte lacunae.According to this process, chondrocyte colony-like clusters could be divided into four stages.Conclusions: Chondrocyte colony-like clusters mainly formed during the development of OA of OARSI grades 3 and 4 could cause the cartilage tissue to become looser and more porous, with more severe cartilage degeneration.

Asporin regulated by miR-26b-5p mediates chondrocyte senescence and exacerbates osteoarthritis progression via TGF-β1/Smad2 pathway

Rheumatology ◽  
2021 ◽  
Author(s):  
Liangliang Liu ◽  
Chang Zhao ◽  
Haiyan Zhang ◽  
Yuheng Lu ◽  
Bingsheng Luo ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Medial Meniscus ◽  
Articular Chondrocytes ◽  
Cartilage Damage ◽  
Cartilage Degeneration ◽  
Research Society ◽  
Osteoarthritis Progression ◽  
Osteoarthritis Research Society ◽  
Tgf Β1

Abstract Objectives This study aimed to investigate the role and mechanism of asporin in modulating chondrocyte senescence in osteoarthritis (OA) pathology. Methods Asporin and senescence-related hallmark expression were examined in human and experimental OA mouse cartilage samples. Twelve-week-old male C57 mice were administered with recombinant protein (rm-asporin)- or asporin-siRNA-expressing lentiviruses via intra-articular injection once a week after destabilization of the medial meniscus (DMM) surgery to induce OA. Cartilage damage was measured using the Osteoarthritis Research Society International score. Senescence-associated β-galactosidase (SA-βGal) staining, γH2AX, p21, and p16INK4a were analyzed by immunofluorescence staining and western blot to assess the specific role of asporin in chondrocyte senescence. The TGF-β1/Smad2 signaling pathway and miR-26b-5p were further evaluated to explore the mechanism of asporin in OA. Results Asporin was upregulated in articular chondrocytes of OA patients and DMM mice and accompanied by accumulation of senescent cells. Asporin overexpression exaggerated OA progression, whereas silencing asporin restored chondrocyte homeostasis and deferred chondrocyte senescence, leading to markedly attenuated DMM-induced OA. Cellular and molecular analyses showed that asporin can be inhibited by miR-26b-5p, which was significantly downregulated in OA cartilage, leading to exacerbation of experimental OA partially through inhibition of TGF-β1/Smad2 signaling in chondrocytes. Conclusions Our findings indicate that asporin plays an essential role in chondrocyte senescence and OA pathogenesis. Upregulated by miR-26b-5p, asporin inhibits the TGF-β1/Smad2 pathway to accelerate chondrocyte senescence and exacerbate cartilage degeneration. Targeting the miR-26b-5p/asporin/Smad2 axis may serve as a practical therapeutic strategy to delay chondrocyte senescence and OA development.

Experimental Observation of the Sequence of Tibial Plateau Chondrocyte and Matrix Degeneration in Spontaneous Osteoarthritis in Guinea Pigs

2020 ◽  
Author(s):  
XIAOJIAN WANG ◽  
XIAOJIAN Wang ◽  
Lei Wei ◽  
Yan Xue ◽  
Rong-shan Li
Keyword(s):  
Knee Osteoarthritis ◽  
Guinea Pigs ◽  
Tibial Plateau ◽  
Caspase 3 ◽  
Physiological State ◽  
Research Society ◽  
Cartilage Tissue ◽  
Knee Oa ◽  
The Matrix ◽  
Osteoarthritis Research Society

Abstract Background To observe the sequence of chondrocyte degeneration and matrix degradation in the superficial surface cartilage of the tibial plateau in guinea pigs with spontaneous knee osteoarthritis (OA).Methods Forty guinea pigs were euthanized at the ages of 10 months (n=20) and 12 months (n=20). The degree of degeneration of the tibial plateau cartilage was evaluated by Osteoarthritis Research Society International (OARSI) score.The levels of MMP-13 and Caspase-3 in the chondrocytes were detected by immunohistochemistry (IHC). The serum concentration of CTX-II was measured and compared.Western blot analysis was used to detect the levels of MMP-13 and Caspase-3 in the cartilage tissue.Results The OARSI score in the 10-month-old group(6.4±1.7) was lower than that in the 12-month-old group(12.7±3.2)(P＜0.05). Immunohistochemical staining confirmed the levels of MMP-13(10-month-old,6.1±2.0;12-month-old,5.8±1.6) and Caspase-3(10-month-old,2.6±0.6;12-month-old,2.8±0.9) in two groups appeared to be nonsignificant (all P＜0.05).The serum CTX-II in the 10-month-old group(8.6±1.2) was lower than that in the 12-month-old group(13.7±2.3) (P＜0.05). The western blot results confirmed the levels of MMP-13(10-month-old,0.82±0.21;12-month-old,0.86±0.27) and Caspase-3(10-month-old,0.22±0.07;12-month-old,0.20±0.08) in two groups appeared to be nonsignificant (all P＜0.05).Conclusion The superficial chondrocytes of the tibial plateau first appeared to be hypertrophic and then apoptotic, and the matrix was further degraded when spontaneous knee osteoarthritis occurred in guinea pigs.Changes in the physiological state of chondrocytes are the initiating factors in the pathogenesis of knee OA.

scholarly journals Meloxicam ameliorates the cartilage and subchondral bone deterioration in monoiodoacetate-induced rat osteoarthritis

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3185 ◽  
Author(s):  
Előd Nagy ◽  
Enikő Vajda ◽  
Camil Vari ◽  
Sándor Sipka ◽  
Ana-Maria Fárr ◽  
...  
Keyword(s):  
Subchondral Bone ◽  
Low Dose ◽  
Late Phase ◽  
Cartilage Degeneration ◽  
Research Society ◽  
Bone Lesions ◽  
High Dose ◽  
Low Grade ◽  
Male Wistar Rats ◽  
Osteoarthritis Research Society

ObjectiveThis study aimed to quantify the cartilage- and subchondral bone-related effects of low-dose and high-dose meloxicam treatment in the late phase of mono-iodoacetate-induced osteoarthritis of the stifle.MethodsThirty-four male Wistar rats received intra-articular injection of mono-iodoacetate to trigger osteoarthritis; 10 control animals (Grp Co) received saline. The mono-iodoacetate-injected rats were assigned to three groups and treated from week 4 to the end of week 7 with placebo (Grp P,n = 11), low-dose (GrpM Lo, 0.2 mg/kg,n = 12) or high-dose (GrpM Hi, 1 mg/kg,n = 11) meloxicam. After a period of 4 additional weeks (end of week 11) the animals were sacrificed, and the stifle joints were examined histologically and immunohistochemically for cyclooxygenase 2, in conformity with recommendations of the Osteoarthritis Research Society International. Serum cytokines IL-6, TNFα and IL-10 were measured at the end of weeks 3, 7, and 11.ResultsCompared with saline-treated controls, animals treated with mono-iodoacetate developed various degrees of osteoarthritis. The cartilage degeneration score and the total cartilage degeneration width were significantly lower in both the low-dose (p = 0.012 andp = 0.014) and high-dose (p = 0.003 andp = 0.006) meloxicam-treated groups than in the placebo group. In the subchondral bone, only high-dose meloxicam exerted a significant protective effect (p = 0.011). Low-grade Cox-2 expression observed in placebo-treated animals was abolished in both meloxicam groups. Increase with borderline significance of TNFα in GrpP from week 3 to week 7 (p = 0.049) and reduction of IL-6 in GrpM Lo from week 3 to week 11 (p = 0.044) were observed.ConclusionIn this rat model of osteoarthritis, both low-dose and high-dose meloxicam had a chondroprotective effect, and the high dose also protected against subchondral bone lesions. The results suggest a superior protection of the high-dose meloxicam arresting the low-grade inflammatory pathway accompanied by chronic cartilage deterioration.

scholarly journals Pattern of Inflammatory Molecules in Cartilage of the Impingement Zone in FAI Hips Suggests Origin of Hip Degeneration

2019 ◽  
Vol 7 (7_suppl5) ◽  
pp. 2325967119S0032
Author(s):  
Cecilia Pascual-Garrido ◽  
Masahiko Haneda ◽  
Muhammad Farooq Rai ◽  
Robert H. Brophy ◽  
John C. Clohisy
Keyword(s):  
Cartilage Damage ◽  
Hip Osteoarthritis ◽  
Developmental Dysplasia ◽  
Mankin Score ◽  
Junction Area ◽  
Hip Impingement ◽  
Α Angle ◽  
Inflammatory Molecules ◽  
Head Neck ◽  
Neck Junction

Objectives: Femoroacetabular impingement (FAI) is considered a common cause of articular cartilage damage and early hip osteoarthritis (OA) in the young-adult patients. Molecular inflammation is believed to be one of the main initiators of hip OA. Matrix metalloproteinase (MMP)-13 and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 are known to function as extracellular matrix degrading enzymes in OA joints and have been shown to increase during the process of OA onset. Interleukin (IL)-1β is considered one of the key cytokines involved in the pathogenesis of OA. The aim of this study is to characterize inflammation and early OA pathways in cartilage from the head-neck impingement area in patients with symptomatic FAI cam. Methods: Cartilage samples were obtained in the head neck-junction area from 37 patients undergoing hip surgery between May 2017 and July 2018. Nine patients had a clinical diagnosis of FAI cam (FAI cam) and 15 patients presented advanced OA secondary to FAI cam (OA FAI). These cartilage samples were compared to cartilage samples obtained from similar head neck-junction area from 13 patients with advanced OA secondary to developmental dysplasia of the hip with no impingement (OA DDH). Radiographically, the α-angle was utilized to confirm hip impingement. All histological sections were stained with Safranin-O to assess cartilage degeneration. OARSI grade and Mankin score were used to quantify degenerative OA changes. Immunohistochemistry was performed for IL-1β, MMP-13 and ADAMTS-4. Quantification of immunopositive cells was performed in a blinded fashion. One-way analysis of variance with Tukey’s post hoc test was applied to analyze differences between three groups. Results: FAI cam patients were significantly younger than OA FAI patients (p<0.001) and OA DDH patients (p=0.0461) (Table 1). The average α-angle was significantly higher in the FAI cam and OA FAI groups than the OA DDH group (p<0.001). Cartilage samples from the FAI cam and the OA FAI groups showed degenerative changes. The average OARSI grade was significantly (p<0.01) higher in FAI cam (4.0±0.4) and OA FAI (3.6±0.9) compared to OA DDH (2.2±0.6). The average Mankin score was significantly (p<0.001) higher in FAI cam (7.6±1.2) and OA FAI (6.9±1.8) than OA DDH (4.1±0.7). IL-1β was expressed in cartilage samples from all groups, although the pattern varied.IL-1β was expressed mainly in the superficial layer in the OA DDH group but throughout all cartilage layers in the FAI cam and OA FAI groups. The % immunopositive cells were significantly (p<0.001) higher in FAI cam (58.1±8.9) and OA FAI (71.3±12.4) than OA DDH (28.9±6.3). Similar pattern of distribution was observed for MMP-13 (72.7±11.3, 70.2±18.2 vs 38.0±8.6; p<0.001, p<0.001) and ADAMTS-4 (73.1±7.3, 82.0±12.3 vs 45.3±12.7; p<0.001, p<0.001) (Figure 1). Conclusion: Osteoarthritic changes are evident in the cartilage from the head-neck area of patients with FAI cam morphology. Inflammatory molecules were evident in both early and late stages of hip impingement, suggesting the head-neck impingement area is a potential mediator of inflammation and joint degeneration. [Figure: see text][Table: see text]

scholarly journals Impact of Controlling Abnormal Joint Movement on the Effectiveness of Subsequent Exercise Intervention in Mouse Models of Early Knee Osteoarthritis

Cartilage ◽  
2019 ◽  
pp. 194760351988500
Author(s):  
Yuichiro Oka ◽  
Kenji Murata ◽  
Takuma Kano ◽  
Kaichi Ozone ◽  
Kohei Arakawa ◽  
...  
Keyword(s):  
Mechanical Stress ◽  
Exercise Intervention ◽  
Cruciate Ligament ◽  
Cartilage Degeneration ◽  
Research Society ◽  
Joint Movement ◽  
Knee Oa ◽  
Osteoarthritis Research Society ◽  
Anterior Cruciate ◽  
Safranin O

Objective Moderate mechanical stress is necessary for preserving the cartilage. The clinician empirically understands that prescribing only exercise will progress osteoarthritis (OA) for knee OA patients with abnormal joint movement. When prescribing exercise for OA, we hypothesized that degeneration of articular cartilage could be further prevented by combining interventions with the viewpoint of normalizing joint movement. Design Twelve-week-old ICR mice underwent anterior cruciate ligament transection (ACL-T) surgery in their right knee and divided into 4 groups: ACL-T, controlled abnormal joint movement (CAJM), ACL-T with exercise (ACL-T/Ex), CAJM with exercise (CAJM/Ex). Animals in the walking group were subjected to treadmill exercise 6 weeks after surgery, which included walking for 18 m/min, 30 min/d, 3 d/wk for 4 weeks. Joint instability was measured by anterior drawer test, and safranin-O staining and immunohistochemical staining were performed. Results OARSI (Osteoarthritis Research Society International) score of ACL-T/Ex group showed highest among 4 groups ( P < 0.001). And CAJM/Ex group was lower than ACL-T/Ex group. Positive cell ratio of IL-1β and MMP-13 in CAJM/Ex group was lower than ACL-T/Ex group ( P < 0.05). Conclusions We found that the state of the intra-articular environment can greatly influence the effect of exercise on cartilage degeneration, even if exercise is performed under the same conditions. In the CAJM/Ex group where joint movement was normalized, abnormal mechanical stress such as shear force and compression force accompanying ACL cutting was alleviated. These findings may highlight the need to consider an intervention to correct abnormal joint movement before prescribing physical exercise in the treatment of OA.

scholarly journals Post-traumatic osteoarthritis development is not modified by postnatal chondrocyte deletion of Ccn2

2020 ◽  
Vol 13 (7) ◽  
pp. dmm044719 ◽  
Author(s):  
Craig M. Keenan ◽  
Lorenzo Ramos-Mucci ◽  
Ioannis Kanakis ◽  
Peter I. Milner ◽  
Andrew Leask ◽  
...  
Keyword(s):  
Articular Chondrocytes ◽  
Cartilage Degeneration ◽  
Research Society ◽  
Knee Joints ◽  
Matricellular Protein ◽  
Micro Computed Tomography ◽  
Non Invasive ◽  
Post Surgery ◽  
Osteoarthritis Research Society ◽  
Post Traumatic

ABSTRACTCCN2 is a matricellular protein involved in several crucial biological processes. In particular, CCN2 is involved in cartilage development and in osteoarthritis. Ccn2 null mice exhibit a range of skeletal dysmorphisms, highlighting its importance in regulating matrix formation during development; however, its role in adult cartilage remains unclear. The aim of this study was to determine the role of CCN2 in postnatal chondrocytes in models of post-traumatic osteoarthritis (PTOA). Ccn2 deletion was induced in articular chondrocytes of male transgenic mice at 8 weeks of age. PTOA was induced in knees either surgically or non-invasively by repetitive mechanical loading at 10 weeks of age. Knee joints were harvested, scanned with micro-computed tomography and processed for histology. Sections were stained with Toluidine Blue and scored using the Osteoarthritis Research Society International (OARSI) grading system. In the non-invasive model, cartilage lesions were present in the lateral femur, but no significant differences were observed between wild-type (WT) and Ccn2 knockout (KO) mice 6 weeks post-loading. In the surgical model, severe cartilage degeneration was observed in the medial compartments, but no significant differences were observed between WT and Ccn2 KO mice at 2, 4 and 8 weeks post-surgery. We conclude that Ccn2 deletion in chondrocytes does not modify the development of PTOA in mice, suggesting that chondrocyte expression of CCN2 in adults is not a crucial factor in protecting cartilage from the degeneration associated with PTOA.This article has an associated First Person interview with the first author of the paper.

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