scholarly journals Mineral crystal thickness in calcified cartilage and subchondral bone in healthy and osteoarthritic knees

2021 ◽  
Author(s):  
Mikko A.J. Finnilä ◽  
Shuvashis Das Gupta ◽  
Mikael J. Turunen ◽  
Iida Kestilä ◽  
Aleksandra Turkiewicz ◽  
...  
Keyword(s):  
Subchondral Bone ◽  
Wide Spectrum ◽  
Disease Process ◽  
Lateral Compartment ◽  
Medial Compartment ◽  
Joint Disease ◽  
Crystal Thickness ◽  
Knee Oa ◽  
Mineral Crystal ◽  
Calcified Cartilage

Osteoarthritis (OA) is the most common joint disease globally. In OA, articular cartilage degradation is often accompanied with sclerosis of the subchondral bone. However, the association between OA and tissue mineralization at the nanostructural level is currently not understood. Especially, it is technically challenging to identify calcified cartilage, where relevant but poorly understood pathological processes like tidemark multiplication and advancement occur. Here, we used state-of-the art micro-focus small-angle X-ray scattering with high 5μm spatial resolution to determine mineral crystal thickness in human subchondral bone and calcified cartilage. Specimens with a wide spectrum of OA severities were acquired from the medial and lateral compartments of medial compartment knee OA patients (n=15) and cadaver knees (n=10). For the first time, we identified a well-defined layer of calcified cartilage associated with pathological tidemark multiplication, containing 0.32nm thicker crystals compared to the rest of calcified cartilage. In addition, we found 0.2nm thicker mineral crystals in both tissues of the lateral compartment in OA compared with healthy knees, indicating a loading-related disease process since the lateral compartment is typically less loaded in medial compartment knee OA. Furthermore, the crystal thickness of the subchondral bone was lower with increasing histopathological OA severity. In summary, we report novel changes in mineral crystal thickness during OA. Our data suggest that unloading in the knee is associated with the growth of mineral crystals, which is especially evident in the calcified cartilage. In the subchondral bone, mineral crystals become thinner with increasing OA severity, which indicates new bone formation with sclerosis.

scholarly journals Mineral crystal thickness in calcified cartilage and subchondral bone in human end-stage knee osteoarthritis and controls

2019 ◽  
Vol 27 ◽  
pp. S180-S181
Author(s):  
M.A. Finnilä ◽  
M. Turunen ◽  
I. Kestilä ◽  
E. Folkesson ◽  
N. Ali ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Subchondral Bone ◽  
Crystal Thickness ◽  
Mineral Crystal ◽  
Calcified Cartilage ◽  
End Stage

scholarly journals Tissue Modification of the Lateral Compartment of the Tibio-Femoral Joint Following In Vivo Varus Loading in the Rat

2012 ◽  
Vol 134 (10) ◽  
Author(s):  
M. L. Roemhildt ◽  
B. D. Beynnon ◽  
M. Gardner-Morse ◽  
K. Anderson ◽  
G. J. Badger
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
Compressive Loading ◽  
Compressive Load ◽  
Lateral Compartment ◽  
Peripheral Region ◽  
Degenerative Changes ◽  
Medial Compartment ◽  
Compressive Loads

This study describes the first application of a varus loading device (VLD) to the rat hind limb to study the role of sustained altered compressive loading and its relationship to the initiation of degenerative changes to the tibio-femoral joint. The VLD applies decreased compressive load to the lateral compartment and increased compressive load to the medial compartment of the tibio-femoral joint in a controlled manner. Mature rats were randomized into one of three groups: unoperated control, 0% (sham), or 80% body weight (BW). Devices were attached to an animal’s leg to deliver altered loads of 0% and 80% BW to the experimental knee for 12 weeks. Compartment-specific material properties of the tibial cartilage and subchondral bone were determined using indentation tests. Articular cartilage, calcified cartilage, and subchondral bone thicknesses, articular cartilage cellularity, and degeneration score were determined histologically. Joint tissues were sensitive to 12 weeks of decreased compressive loading in the lateral compartment with articular cartilage thickness decreased in the peripheral region, subchondral bone thickness increased, and cellularity of the midline region decreased in the 80% BW group as compared to the 0% BW group. The medial compartment revealed trends for diminished cellularity and aggregate modulus with increased loading. The rat-VLD model provides a new system to evaluate altered quantified levels of chronic in vivo loading without disruption of the joint capsule while maintaining full use of the knee. These results reveal a greater sensitivity of tissue parameters to decreased loading versus increased loading of 80% BW for 12 weeks in the rat. This model will allow future mechanistic studies that focus on the initiation and progression of degenerative changes with increased exposure in both magnitude and time to altered compressive loads.

scholarly journals Risk factors and molecular entities of the etiopathogenesis of the knee osteoarthritis (literature review)

2021 ◽  
Vol 27 (1) ◽  
pp. 112-120
Author(s):  
V.B. Novakov ◽  
◽  
O.N. Novakova ◽  
M.I. Churnosov ◽  
◽  
...  
Keyword(s):  
Risk Factors ◽  
Literature Review ◽  
Knee Osteoarthritis ◽  
Subchondral Bone ◽  
Molecular Mechanisms ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Bibliographic Databases ◽  
Joint Involvement ◽  
Knee Oa

Introduction Osteoarthritis (OA) is a heterogenic group of disorders of different etiology with similar biological, morphological and clinical manifestations and outcomes. OA is now considered a disease of the whole joint, including alterations in the articular cartilage, subchondral bone, synovial membrane, ligaments, capsule and periarticular muscles. OA of the knee as the most commonly affected joint accounts for the great medical, medical, social and economic impact. Material and methods A literature review assessing Russian and foreign studies on molecular mechanisms of etiology and pathogenesis of knee OA identified a set of factors for which there was consistent evidence for their association with onset of knee OA. A search of studies published in Russian and in English for the last ten years was conducted using bibliographic databases, including PubMed, PubMedCentral, GoogleScholar, eLIBRARY. Search terms included 'knee osteoarthritis', 'etiology', 'pathogenesis', 'risk factors'. Results Review of the literature showed that patients with knee OA are characterized by changes in cartilage, subchondral bone, synovium, suggesting common mechanisms of joint degeneration during OA development. Osteoarthritis (OA) is multifactorial in origin and closely associated with a wide spectrum of local (previous injury, muscle weakness, knee malalignment, knee surgeries, abnormal mechanical loading, excessive high impact sports, occupational physical activities) and systemic risk factors (advanced age, female sex, height, greater body mass index and obesity, hormone status, family history, mineral bone density, vitamin D deficiency, ethnicity). The prevalence of the knee OA and patterns of joint involvement vary among different racial and ethnic groups. Conclusion The literature review allowed us to identify the molecular mechanisms of etiopathogenesis of knee OA and the major risk factors for the pathology.

scholarly journals β2-Adrenoceptor Deficiency Results in Increased Calcified Cartilage Thickness and Subchondral Bone Remodeling in Murine Experimental Osteoarthritis

2022 ◽  
Vol 12 ◽  
Author(s):  
Gundula Rösch ◽  
Dominique Muschter ◽  
Shahed Taheri ◽  
Karima El Bagdadi ◽  
Christoph Dorn ◽  
...  
Keyword(s):  
Body Weight ◽  
Bone Remodeling ◽  
Subchondral Bone ◽  
Plate Thickness ◽  
Cathepsin K ◽  
Cartilage Degeneration ◽  
Synovial Inflammation ◽  
Serum Leptin ◽  
Knee Oa ◽  
Calcified Cartilage

PurposeRecent studies demonstrated a contribution of adrenoceptors (ARs) to osteoarthritis (OA) pathogenesis. Several AR subtypes are expressed in joint tissues and the β2-AR subtype seems to play a major role during OA progression. However, the importance of β2-AR has not yet been investigated in knee OA. Therefore, we examined the development of knee OA in β2-AR-deficient (Adrb2-/-) mice after surgical OA induction.MethodsOA was induced by destabilization of the medial meniscus (DMM) in male wildtype (WT) and Adrb2-/- mice. Cartilage degeneration and synovial inflammation were evaluated by histological scoring. Subchondral bone remodeling was analyzed using micro-CT. Osteoblast (alkaline phosphatase - ALP) and osteoclast (cathepsin K - CatK) activity were analyzed by immunostainings. To evaluate β2-AR deficiency-associated effects, body weight, sympathetic tone (splenic norepinephrine (NE) via HPLC) and serum leptin levels (ELISA) were determined. Expression of the second major AR, the α2-AR, was analyzed in joint tissues by immunostaining.ResultsWT and Adrb2-/- DMM mice developed comparable changes in cartilage degeneration and synovial inflammation. Adrb2-/- DMM mice displayed elevated calcified cartilage and subchondral bone plate thickness as well as increased epiphyseal BV/TV compared to WTs, while there were no significant differences in Sham animals. In the subchondral bone of Adrb2-/- mice, osteoblasts activity increased and osteoclast activity deceased. Adrb2-/- mice had significantly higher body weight and fat mass compared to WT mice. Serum leptin levels increased in Adrb2-/- DMM compared to WT DMM without any difference between the respective Shams. There was no difference in the development of meniscal ossicles and osteophytes or in the subarticular trabecular microstructure between Adrb2-/- and WT DMM as well as Adrb2-/- and WT Sham mice. Number of α2-AR-positive cells was lower in Adrb2-/- than in WT mice in all analyzed tissues and decreased in both Adrb2-/- and WT over time.ConclusionWe propose that the increased bone mass in Adrb2-/- DMM mice was not only due to β2-AR deficiency but to a synergistic effect of OA and elevated leptin concentrations. Taken together, β2-AR plays a major role in OA-related subchondral bone remodeling and is thus an attractive target for the exploration of novel therapeutic avenues.

Regional Cartilage Thinning Occurs First in the Walking Weight Bearing Regions of the Femur in Medial Compartment Knee Osteoarthritis

2008 ◽  
Author(s):  
Jennifer C. Erhart ◽  
Anne Mündermann ◽  
Seungbum Koo ◽  
Ben Merrick ◽  
Andrew Deagon ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Femoral Condyle ◽  
Weight Bearing ◽  
Lateral Compartment ◽  
Medial Compartment ◽  
Treatment Interventions ◽  
Knee Oa ◽  
Highest Weight ◽  
Kellgren And Lawrence ◽  
New Treatment

Osteoarthritis (OA) of the knee affects an estimated 20–40% of individuals over the age of 65 [1], and is nearly 10 times more common in the medial compartment than the lateral compartment [2]. Plain radiography measurements using the Kellgren and Lawrence (KL) scale have been the gold standard for diagnosis of knee osteoarthritis [3]. However, for new treatment interventions for medial compartment knee OA such as load modifying footwear, it would be important to know if the disease-related cartilage loss in the medial compartment occurs initially and predominantly in regions that are weight bearing during walking. Because walking results in highest weight bearing occurring in the anterior and middle regions of the femoral condyle and the anterior region of the tibial plateau, seeing a pattern of thinning in these areas would suggest that walking is an important activity for understanding both the cause and treatment of osteoarthritis.

Decrease in serum level of matrix metalloproteinases is predictive of the disease-modifying effect of osteoarthritis drugs assessed by quantitative MRI in patients with knee osteoarthritis

2010 ◽  
Vol 69 (12) ◽  
pp. 2095-2101 ◽  
Author(s):  
J-P Pelletier ◽  
J-P Raynauld ◽  
J Caron ◽  
F Mineau ◽  
F Abram ◽  
...  
Keyword(s):  
Lateral Compartment ◽  
Cartilage Volume ◽  
Medial Compartment ◽  
Phase Iii ◽  
Volume Loss ◽  
Knee Oa ◽  
Disease Modifying ◽  
Baseline Levels ◽  
Cartilage Volume Loss ◽  
Over Time

ObjectivesTo explore the impact of disease-modifying osteoarthritis drug (DMOAD) treatment on biomarker levels and their correlation with cartilage volume loss and disease symptoms in a 2-year phase III clinical trial in patients with knee OA.Methods161 patients with knee OA (according-to-protocol population) were selected from a 2-year DMOAD trial studying the effect of licofelone (200 mg twice daily) versus naproxen (500 mg twice daily). Clinical evaluation of patients was carried out using the Western Ontario and McMaster Universities (WOMAC) questionnaire. Biomarker measurements of matrix metalloproteinase (MMP)-1, MMP-3, interleukin (IL)-6, C reactive protein (CRP), cartilage oligomeric matrix protein (COMP) and type I collagen C-terminal telopeptide (CTX-I) in serum, type II collagen C-terminal telopeptide (CTX-II) in urine, and knee MRI were performed at baseline and 2 years.ResultsOver time an increase occurred in all biomarker levels with the exception of IL-6, CRP and CTX-II which decreased. The increase in MMP-1 and MMP-3 was significantly less (p=0.05; p<0.01, respectively) in the licofelone group. The baseline MMP-1 level was significantly but inversely predictive of cartilage volume loss for the medial compartment in both univariate (p=0.04) and multivariate (p≤0.04) regression analyses, and COMP, a predictor for the lateral compartment, in both univariate and multivariate models (p<0.01). Baseline levels of IL-6 and CRP also showed a significant relationship with volume loss for the medial compartment (univariate analysis, p=0.04 and p=0.01, respectively; multivariate analysis, p=0.03, p=0.01). A significant association (univariate) was observed between the change in the levels of MMP-1 (p=0.03) and MMP-3 (p=0.02) and cartilage volume loss (lateral compartment) over 2 years. Baseline levels of CTX-I correlated (p=0.02) with an increase in the size of the bone marrow lesion in the medial compartment. The baseline CRP levels correlated with worsening of symptoms: WOMAC total index (p<0.01), pain (p<0.01) and function (p<0.01).ConclusionHigher baseline values of IL-6, CRP and COMP are predictive of greater risk of cartilage loss in OA. However, over time a reduction in MMP-1 and MMP-3 levels correlated best with reduction in cartilage volume loss and the effect of drug treatment. Baseline CRP was found to be a good predictor of the symptomatic response to treatment.

scholarly journals Risk Factors for Radiographic Tibiofemoral Knee Osteoarthritis: The Wuchuan Osteoarthritis Study

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Jianhao Lin ◽  
Rujun Li ◽  
Xiaozheng Kang ◽  
Hu Li
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Knee Osteoarthritis ◽  
Weight Bearing ◽  
Lateral Compartment ◽  
Activity Level ◽  
Medial Compartment ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Knee Oa

Objective. To investigate the risk factors of radiographic tibiafemoral knee osteoarthritis (OA).Methods. A population-based cross-sectional survey was conducted in Wuchuan County. A questionnaire and bilateral weight-bearing posterior-anterior semi-flexed knee radiographs were completed and read for Kellgren and Lawrence (K/L) grade and joint space narrowing (JSN; 0–3 scale) in each compartment. An logistic regression analysis was performed for radiographic tibiafemoral, lateral compartment, and medial compartment knee OA, respectively. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated.Results. Age, sex, and knee injury were strongly associated with tibiafemoral, lateral and medial compartment knee OA. BMI also had a dose-response relationship with them. Physical activity level, and physical activity exposure at work, not significantly though, were associated with an elevated risk for this three kinds of knee OA.Conclusions. Physical activity exposure increased the risk of knee OA. It was likely to be the heavier physical activity in Wuchuan osteoarthritis study that counteracted the BMI gap compared with the Beijing and the Framingham OA study. We verified that Chinese had a more valgus alignment of the knee compared with Caucasian population, and this provide a possible explanation why Chinese have a higher prevalence of lateral compartment OA.

Reduction in the Medial Compartment Force Correlates With the Reduction in Knee Adduction Moment Using a Variable-Stiffness Shoe With an Instrumented Knee

2009 ◽  
Author(s):  
Jennifer C. Erhart ◽  
Chris Dyrby ◽  
Darryl D. D’Lima ◽  
Clifford W. Colwell ◽  
Thomas P. Andriacchi
Keyword(s):  
Treatment Outcome ◽  
Variable Stiffness ◽  
Lateral Compartment ◽  
Medial Compartment ◽  
Knee Adduction Moment ◽  
Joint Loading ◽  
Knee Oa ◽  
Total Knee ◽  
Joint Loads

Osteoarthritis (OA) of the knee affects an estimated 20–40% of individuals over the age of 65 [1], and is nearly 10 times more common in the medial compartment than the lateral compartment [2]. Many studies have reported the effectiveness of footwear modifications using laterally-wedged insoles [3,4] and more recently, variable-stiffness soles [5] in reducing the adduction moment at the knee in patients with medial compartment knee OA. The adduction moment is known to be associated with the progression [6] and treatment outcome [7] of medial compartment knee OA, and has been shown to be correlated with medial compartment joint loading [8]. However, the exact changes in medial compartment joint loading in vivo with the variable-stiffness shoe remain unknown. The development of an instrumented total knee implant which has the ability to directly measure tibial forces, and can differentiate between medial and lateral joint loads in vivo during walking [9], allows the testing of changes in the medial compartment loading with an intervention shoe.

scholarly journals POS0375 CHAPERONE-MEDIATED AUTOPHAGY IS A HALLMARK OF JOINT DISEASE IN OSTEOARTHRITIC PATIENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 418.1-418
Author(s):  
I. Lorenzo ◽  
U. Nogueira-Recalde ◽  
N. Oreiro ◽  
J. A. Pinto Tasende ◽  
M. Lotz ◽  
...  
Keyword(s):  
Lateral Meniscus ◽  
Joint Damage ◽  
Joint Disease ◽  
Expression Array ◽  
Knee Oa ◽  
Human Knee Joint ◽  
Gene And Protein Expression ◽  
Functional Consequences ◽  
Chaperone Mediated Autophagy ◽  
Grade Iii

Background:In Osteoarthritis (OA), defects in macroautophagy (autophagy) are evident and precede joint damage. Indeed, pharmacological activation of autophagy protects against joint damage.Objectives:Therefore, identifying hallmarks associated with specific autophagy subtypes could shed light to fundamental mechanisms of joint disease.Methods:A comparative analysis of 35 autophagy genes was performed from blood from the Prospective OA Cohort of A Coruña (PROCOAC). Non-OA subjects (Age:61,44±1,16 years; BMI:25,25±0,52; Females, n=18) and Knee OA subjects (Age:65,50±1,05 years; BMI:29,55±0,67; Females, n=18, OA grade III-IV) were profiled using an autophagy gene expression array by SYBR green qPCR. Confirmatory studies were performed in blood from Non-OA subjects (Age:60,13±1,12 years; BMI:24,85±0,59; Females; n=30) and Knee-OA subjects (Age:68,4±1,11 years; BMI:29,65±0,55; Females; n=30, OA grade III-IV) by Taqman qPCR. The candidate gene was evaluated in human knee joint tissues (cartilage, meniscus, ligaments, synovium) with different KL grades (Age: KL0=28,3±4,50; KL2=77±6,08; KL4=62,3±3,05, n=3) and in both spontaneous aging (2, 6, 12, 18, and 30 months old, n=3) and surgically-induced OA (10 weeks after surgery, n=4) in mice by IHC. The functional consequences were studied in T/C28a2 and primary human OA chondrocytes. Autophagy, FOXO, Chaperone-mediated autophagy (CMA), inflammation, and cellular senescence were analyzing by gene and protein expression. Moreover, oxidative stress and cell death were evaluated by FACS. The contribution of CMA to chondrocyte homeostasis was evaluated by studying the capacity of CMA to restore proteostasis upon autophagy deficiency by siATG5.Results:15 autophagy-related genes were significantly downregulated in blood from knee OA patients compared to non-OA patients. No significant upregulation was found for any studied gene, although a trend towards upregulation was found in genes involved in the mTOR pathway. Four key autophagy-related genes, including ATG16L2, ATG12, ATG4B and MAP1LC3B were found downregulated in knee OA patients. Interestingly, HSP90AA1 and HSPA8, CMA markers involved in stress response and protein folding, were downregulated. Confirmatory studies showed a significant downregulation of MAP1LC3B and HSP90AA1 in blood from knee OA patients. Remarkably, HSP90A was found reduced in femoral cartilage (medial and lateral), meniscus and ACL. Moreover, this reduction was higher in medial cartilage compared to lateral cartilage and meniscus, while in synovial membrane, HSP90A expression was found increased. This expression signature was dependent on OA grade severity. In addition, we observed a decrease of HSP90A with aging and OA in mice. The functional consequences of HSP90AA1 gene silencing are related to an increase in NFκB, MMP13, and p16 expression. Interestingly, LAMP2A, a key CMA mediator, HSPA8, MAP1LC3B and FoxO1 expression were upregulated in chondrocytes with HSP90AA1 deficiency, which might indicate an early response to maintain homeostasis. On the other hand, LAMP2A protein is decreased upon HSP90AA1 deficiency, while LC3II and p62 were increased, indicating a failure in the autophagy flux that leads to impaired lysosomal degradation.Moreover, p21, p16 and prbS6 were increased upon HSP90AA1 deficiency, besides increasing mitochondrial ROS production and apoptosis. ATG5 silencing blocks autophagy by reducing LC3II and increasing prbs6, p62, p16 and p21. Interestingly, LAMP2A and HSP90A were found increased, indicating a possible compensative activation of CMA in response to autophagy defects. These results support that HSP90A has an important role in chondrocyte homeostasis by participating in the cross-talk between CMA and autophagy.Conclusion:Taking together, we identified HSP90A, a CMA regulator, as critical in chondrocyte homeostasis. These disease mechanisms are relevant in OA and constitute hallmarks potentially useful to prevent OA progression.References:[1]Caramés B, et al. Arthritis Rheum. 2010, 2015;[2]Caramés B, et al. Ann Rheum Dis. 2012.Disclosure of Interests:None declared

scholarly journals Small Noncoding RNAs in Knee Osteoarthritis: The Role of MicroRNAs and tRNA-Derived Fragments

2021 ◽  
Vol 22 (11) ◽  
pp. 5711
Author(s):  
Julian Zacharjasz ◽  
Anna M. Mleczko ◽  
Paweł Bąkowski ◽  
Tomasz Piontek ◽  
Kamilla Bąkowska-Żywicka
Keyword(s):  
Knee Osteoarthritis ◽  
Noncoding Rnas ◽  
Pathological Process ◽  
Joint Disease ◽  
Limited Information ◽  
Genetic Changes ◽  
Small Noncoding Rnas ◽  
Knee Oa ◽  
Cartilage Homeostasis

Knee osteoarthritis (OA) is a degenerative knee joint disease that results from the breakdown of joint cartilage and underlying bone, affecting about 3.3% of the world's population. As OA is a multifactorial disease, the underlying pathological process is closely associated with genetic changes in articular cartilage and bone. Many studies have focused on the role of small noncoding RNAs in OA and identified numbers of microRNAs that play important roles in regulating bone and cartilage homeostasis. The connection between other types of small noncoding RNAs, especially tRNA-derived fragments and knee osteoarthritis is still elusive. The observation that there is limited information about small RNAs different than miRNAs in knee OA was very surprising to us, especially given the fact that tRNA fragments are known to participate in a plethora of human diseases and a portion of them are even more abundant than miRNAs. Inspired by these findings, in this review we have summarized the possible involvement of microRNAs and tRNA-derived fragments in the pathology of knee osteoarthritis.

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