Aging Cartilage in Wild-Type Mice: An Observational Study

Cartilage ◽  
2020 ◽  
pp. 194760352092671
Author(s):  
Joulnar Akoum ◽  
Khadija Tahiri ◽  
Marie-Thérèse Corvol ◽  
Didier Borderie ◽  
François Étienne ◽  
...  
Keyword(s):  
Walking Speed ◽  
Articular Surface ◽  
Type Ii Collagen ◽  
Research Society ◽  
Male Mice ◽  
Wild Type ◽  
Calcified Cartilage ◽  
Age Related ◽  
Wild Type Male ◽  
Osteoarthritis Research Society

Objective To describe the spontaneous evolution of age-related changes affecting knee joint articular cartilage, walking speed and a serum biomarker of cartilage remodeling in C57BL/6-JRj wild-type male mice. Design Histological changes were assessed by the Osteoarthritis Research Society International (OARSI) score (0=normal, 6=vertical clefts/erosion to the calcified cartilage extending >75% of the articular surface) in newborn, 1-week- and 1-, 3-, 6-, 9- and 12-month-old C57BL/6-JRj wild-type male mice, walking speed by the Locotronic system, and serum C-terminal telopeptide of type II collagen (CTX-II) content by ELISA in 1-, 3-, 6-, and 9-month-old C57BL/6-JRj wild-type male mice. Results Mean (SD) OARSI score significantly increased from 0.2 (0.3) to 1.3 (0.6) ( p=0.03) between 1 and 3 months of age and from 1.3 (0.6) to 3.3 (0.6) ( p=0.04) between 3 and 6 months of age. Mean walking speed was stable between 1 and 6 months of age but significantly decreased from 11.4 (1.8) to 3.2 (0.8) cm.s-1 ( p=0.03) between 6 and 9 months of age. Serum CTX-II content was maximal at 1 month of age, then decreased from 12.2 (8.5) to 2.4 (8.4) pg/ml ( p=0.02) between 1 and 3 months of age, remaining low and stable thereafter. Conclusions C57BL/6-JRj wild-type male mice showed continuously increasing osteoarthritic changes but delayed decreasing walking speed with age. These variations were maximal between 3 and 9 months of age. Maximal serum CTX-II content preceded these changes.

scholarly journals Knee Osteoarthritis Progression Is Delayed in Silent Information Regulator 2 Ortholog 1 Knock-in Mice

2021 ◽  
Vol 22 (19) ◽  
pp. 10685
Author(s):  
Tetsuya Yamamoto ◽  
Nobuaki Miyaji ◽  
Kiminari Kataoka ◽  
Kyohei Nishida ◽  
Kanto Nagai ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Interleukin 1 ◽  
Type Ii Collagen ◽  
Research Society ◽  
Type Ii ◽  
Interleukin 1 Beta ◽  
Wild Type ◽  
Osteoarthritis Progression ◽  
Osteoarthritis Research Society ◽  
Wild Type Control

Overexpression of silent information regulator 2 ortholog 1 (SIRT1) is associated with beneficial roles in aging-related diseases; however, the effects of SIRT1 overexpression on osteoarthritis (OA) progression have not yet been studied. The aim of this study was to investigate OA progression in SIRT1-KI mice using a mouse OA model. OA was induced via destabilization of the medial meniscus using 12-week-old SIRT1-KI and wild type (control) mice. OA progression was evaluated histologically based on the Osteoarthritis Research Society International (OARSI) score at 4, 8, 12, and 16 weeks after surgery. The production of SIRT1, type II collagen, MMP-13, ADAMTS-5, cleaved caspase 3, Poly (ADP-ribose) polymerase (PARP) p85, acetylated NF-κB p65, interleukin 1 beta (IL-1β), and IL-6 was examined via immunostaining. The OARSI scores were significantly lower in SIRT1-KI mice than those in control mice at 8, 12, and 16 weeks after surgery. The proportion of SIRT1 and type II collagen-positive-chondrocytes was significantly higher in SIRT1-KI mice than that in control mice. Moreover, the proportion of MMP-13-, ADAMTS-5-, cleaved caspase 3-, PARP p85-, acetylated NF-κB p65-, IL-1β-, and IL-6-positive chondrocytes was significantly lower in SIRT1-KI mice than that in control mice. The mechanically induced OA progression was delayed in SIRT1-KI mice compared to that in control mice. Therefore, overexpression of SIRT1 may represent a mechanism for delaying OA progression.

scholarly journals NPY Deficiency Prevents Postmenopausal Adiposity by Augmenting Estradiol-Mediated Browning

2018 ◽  
Vol 75 (6) ◽  
pp. 1042-1049
Author(s):  
Seongjoon Park ◽  
Erkhembayar Nayantai ◽  
Toshimitsu Komatsu ◽  
Hiroko Hayashi ◽  
Ryoichi Mori ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Fat Metabolism ◽  
Male Mice ◽  
Wild Type ◽  
Male And Female ◽  
Female Mice ◽  
Age Related ◽  
Promising Target ◽  
Intracellular Mechanism

Abstract The orexigenic hormone neuropeptide Y (NPY) plays a pivotal role in the peripheral regulation of fat metabolism. However, the mechanisms underlying the effects of sex on NPY function have not been extensively analyzed. In this study, we examined the effects of NPY deficiency on fat metabolism in male and female mice. Body weight was slightly decreased, whereas white adipose tissue (WAT) mass was significantly decreased as the thermogenic program was upregulated in NPY-/- female mice compared with that in wild-type mice; these factors were not altered in response to NPY deficiency in male mice. Moreover, lack of NPY resulted in an increase in luteinizing hormone (LH) expression in the pituitary gland, with concomitant activation of the estradiol-mediated thermogenic program in inguinal WAT, and alleviated age-related modification of adiposity in female mice. Taken together, these data revealed a novel intracellular mechanism of NPY in the regulation of fat metabolism and highlighted the sexual dimorphism of NPY as a promising target for drug development to reduce postmenopausal adiposity.

scholarly journals The Inverse OARSI-OMERACT Criteria Is a Valid Indicator of the Clinical Worsening of Knee Osteoarthritis: Data from the Osteoarthritis Initiative

2020 ◽  
pp. jrheum.200145
Author(s):  
Jeffrey B. Driban ◽  
Matthew S. Harkey ◽  
Lori Lyn Price ◽  
Grace H. Lo ◽  
Timothy E. McAlindon
Keyword(s):  
Knee Osteoarthritis ◽  
Knee Pain ◽  
Knee Replacement ◽  
Walking Speed ◽  
Cox Model ◽  
Research Society ◽  
Osteoarthritis Initiative ◽  
Osteoarthritis Research Society ◽  
And Function ◽  
Relationship Of

Objective We assessed if the inverse Osteoarthritis Research Society International (OARSI) and Outcome Measures in Rheumatology (OMERACT) criteria relate to concurrent radiographic knee osteoarthritis (KOA) progression and decline in walking speed, as well as future knee replacement. Methods We conducted knee-based analyses of data from the Osteoarthritis Initiative. All knees had symptomatic OA: at least doubtful radiographic KOA (Kellgren-Lawrence grade ≥ 1) and knee pain ≥ 10/100 (Western Ontario and McMaster Universities Osteoarthritis Index pain) at the 12-month visit. The inverse of the OARSI-OMERACT responder criteria depended on knee pain and function, and global assessment of knee impact. We used generalized linear mixed models to assess the relationship of the inverse OARSI‑OMERACT criteria over 2 years (i.e., 12-month and 36-month visits) with worsening radiographic severity (any increase in Kellgren-Lawrence grade from 12 months to 36 months) and decline in self-selected 20-m walking speed of ≥ 0.1m/s (from 12 months to 36 months). We used a Cox model to assess time to knee replacement during the 6 years after the 36-month visit as an outcome. Results Among the 1746 analyzed, 19% met the inverse OARSI-OMERACT criteria. Meeting the inverse OARSI-OMERACT criteria was associated with almost double the odds of experiencing concurrent worsening in radiographic KOA severity (OR 1.89, 95% CI 1.32–2.70) or decline in walking speed (OR 1.82, 95% CI 1.37–2.40). A knee meeting the inverse OARSI-OMERACT criteria was more likely to receive a knee replacement after the 36-month visit (23%) compared with a nonresponder (10%; HR 2.54, 95% CI 1.89–3.41). Conclusion The inverse OARSI-OMERACT criteria for worsening among people with KOA had good construct validity in relation to clinically relevant outcomes.

scholarly journals Murine fibromodulin: cDNA and genomic structure, and age-related expression and distribution in the knee joint

2001 ◽  
Vol 355 (3) ◽  
pp. 577-585 ◽  
Author(s):  
Anna-Marja K. SÄÄMÄNEN ◽  
Heli J. SALMINEN ◽  
A. Juho RANTAKOKKO ◽  
Dick HEINEGÅRD ◽  
Eero I. VUORIO
Keyword(s):  
Genomic Structure ◽  
Type Ii Collagen ◽  
Type I ◽  
Mrna Levels ◽  
Primary Role ◽  
Type Ii ◽  
Exon 2 ◽  
Collagen Fibrillogenesis ◽  
Calcified Cartilage ◽  
Age Related

The genomic structure of murine fibromodulin was determined, and its age-related expression and distribution were characterized in knee epiphyses, with decorin studied for reference. Fibromodulin, as well as decorin, have roles in collagen fibrillogenesis both in vitro and in vivo. The murine fibromodulin gene, Fmod, was similar with that in other species, with three exons and 86% of the translated sequence in exon 2. The 2.7kb long cDNA contains an open reading frame of 1131nt. Fibromodulin mRNA levels were highest in tissues rich in fibrillar collagens type I or type II. During growth, the distribution of fibromodulin mRNA was similar with that of type II collagen, with the highest levels between 5 days and 1 month of age. Thereafter, the expression of type II collagen declined to a level near the detection limit, whereas the fibromodulin expression decreased less markedly to a level of approx. 35% of maximum, and remained constant throughout the rest of the observation period. In contrast, decorin mRNA levels were the highest in old animals. Pericellular deposition of fibromodulin was strong around the late-hypertrophic chondrocytes of the secondary ossification centre and in the growth plate. In young epiphyses, both fibromodulin and decorin were found interterritorially, mainly in the uncalcified and deep-calcified cartilage. In the old mice, calcified cartilage became enriched with regard to fibromodulin, while, in contrast, decorin deposition diminished, particularly near the tidemark. In the subchondral bone trabeculae, decorin was found in the endosteum of growing, but not in the mature, epiphyses. Differences in the expression and distribution profiles suggest different roles for fibromodulin and decorin in the regulation of collagen fibrillogenesis, maintenance of the fibril organization and matrix mineralization. As fibromodulin is deposited closer to cells than decorin, it may have a primary role in collagen fibrillogenesis, whereas decorin might be involved in the maintenance of fibril structures in the interterritorial matrix.

scholarly journals Pemafibrate Protects against Fatty Acid-Induced Nephropathy by Maintaining Renal Fatty Acid Metabolism

Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 372
Author(s):  
Daiki Aomura ◽  
Makoto Harada ◽  
Yosuke Yamada ◽  
Takero Nakajima ◽  
Koji Hashimoto ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Kidney Disease ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Male Mice ◽  
Histological Findings ◽  
Tubular Injury ◽  
Wild Type ◽  
Wild Type Male ◽  
And Oxidative Stress

As classical agonists for peroxisomal proliferator-activated receptor alpha (PPARα), fibrates activate renal fatty acid metabolism (FAM) and provide renoprotection. However, fibrate prescription is limited in patients with kidney disease, since impaired urinary excretion of the drug causes serious adverse effects. Pemafibrate (PEM), a novel selective PPARα modulator, is mainly excreted in bile, and, thus, may be safe and effective in kidney disease patients. It remains unclear, however, whether PEM actually exhibits renoprotective properties. We investigated this issue using mice with fatty acid overload nephropathy (FAON). PEM (0.5 mg/kg body weight/day) or a vehicle was administered for 20 days to 13-week-old wild-type male mice, which were simultaneously injected with free fatty acid (FFA)-binding bovine serum albumin from day 7 to day 20 to induce FAON. All mice were sacrificed on day 20 for assessment of the renoprotective effect of PEM against FAON. PEM significantly attenuated the histological findings of tubular injury caused by FAON, increased the renal expressions of mRNA and proteins related to FAM, and decreased renal FFA content and oxidative stress. Taken together, PEM exhibits renoprotective effects through the activation and maintenance of renal FAM and represents a promising drug for kidney disease.

scholarly journals Gender- and Age-dependent Changes in Kidney Androgen Protein mRNA Expression in a Knockout Mouse Model for Nephrolithiasis

2002 ◽  
Vol 50 (12) ◽  
pp. 1663-1669 ◽  
Author(s):  
Eleni G. Tzortzaki ◽  
Dayna Glass ◽  
Min Yang ◽  
Andrew P. Evan ◽  
Sharon B. Bledsoe ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Kidney Tissue ◽  
Mouse Kidney ◽  
Male Mice ◽  
Wild Type ◽  
Rt Pcr ◽  
Cytoplasmic Staining ◽  
Female Mice ◽  
Age Dependent ◽  
Wild Type Male

Kidney androgen-regulated protein (Kap) is the most abundant protein in the mouse kidney, but its function is unknown. We previously observed a significant decrease in Kap mRNA expression in whole kidney tissue from male mice with adenine phosphoribosyltransferase (APRT) deficiency and 2,8-dihydroxyadenine (DHA) nephrolithiasis. The disease phenotype is more severe in male mice and is age-dependent. To identify the cellular basis for differential Kap expression, we used in situ hybridization (ISH) and reverse transcription-polymerase chain reaction ISH (RT-PCR ISH) to identify the cell types expressing this mRNA in paraffin-embedded kidney sections. In 1-month-old wild-type male mice, Kap was detected primarily in S3 proximal tubule segments, but expression was very low in female mice. In 1-month-old APRT-deficient male mice, Kap expression was decreased significantly and was undetectable in female mice. Kap mRNA was not detected in 3- or 6-month-old mice using our standard ISH protocol, but we observed intense cytoplasmic staining in S3 proximal tubules in wild-type male mice of these age groups using an improved RT-PCR ISH procedure. Our studies demonstrate age-, gender-, and APRT genotype-dependent changes in Kap mRNA expression in mouse kidney. Kap expression is under multihormonal control, and hormonal changes in DHA-induced nephrolithiasis may account for the decreased Kap expression in APRT-deficient mice.

scholarly journals Soluble syndecan-1 and glycosaminoglycans in preeclamptic and normotensive pregnancies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
H. Hassani Lahsinoui ◽  
F. Amraoui ◽  
L. J. A. Spijkers ◽  
G. J. M. Veenboer ◽  
S. L. M. Peters ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heparan Sulphate ◽  
Activated Partial Thromboplastin Time ◽  
Male Mice ◽  
Wild Type ◽  
Dermatan Sulphate ◽  
Keratan Sulphate ◽  
Blood Pressure Elevation ◽  
Wild Type Male ◽  
Deficient Mice

AbstractPreeclampsia, an important cause of maternal and fetal morbidity and mortality, is associated with increased sFLT1 levels and with structural and functional damage to the glycocalyx contributing to endothelial dysfunction. We investigated glycocalyx components in relation to preeclampsia in human samples. While soluble syndecan-1 and heparan sulphate were similar in plasma of preeclamptic and normotensive pregnant women, dermatan sulphate was increased and keratan sulphate decreased in preeclamptic women. Dermatan sulphate was correlated with soluble syndecan-1, and inversely correlated with blood pressure and activated partial thromboplastin time. To determine if syndecan-1 was a prerequisite for the sFlt1 induced increase in blood pressure in mice we studied the effect of sFlt1 on blood pressure and vascular contractile responses in syndecan-1 deficient and wild type male mice. The classical sFlt1 induced rise in blood pressure was absent in syndecan-1 deficient mice indicating that syndecan-1 is a prerequisite for sFlt1 induced increase in blood pressure central to preeclampsia. The results show that an interplay between syndecan-1 and dermatan sulphate contributes to sFlt1 induced blood pressure elevation in pre-eclampsia.

scholarly journals Genomic modules and intramodular network concordance in susceptible and resilient male mice across models of stress

2021 ◽  
Author(s):  
Salvatore G. Caradonna ◽  
Tie-Yuan Zhang ◽  
Nicholas O’Toole ◽  
Mo-Jun Shen ◽  
Huzefa Khalil ◽  
...  
Keyword(s):  
Gene Networks ◽  
Anxiety And Depression ◽  
Stress Coping ◽  
Housing Conditions ◽  
Male Mice ◽  
Wild Type ◽  
Genomic Signatures ◽  
Gene Coding ◽  
Chronic Social Defeat Stress ◽  
Wild Type Male

AbstractThe multifactorial etiology of stress-related disorders necessitates a constant interrogation of the molecular convergences in preclinical models of stress that use disparate paradigms as stressors spanning from environmental challenges to genetic predisposition to hormonal signaling. Using RNA-sequencing, we investigated the genomic signatures in the ventral hippocampus common to mouse models of stress. Chronic oral corticosterone (CORT) induced increased anxiety- and depression-like behavior in wild-type male mice and male mice heterozygous for the gene coding for brain-derived neurotrophic factor Val66Met, a variant associated with genetic susceptibility to stress. In a separate set of male mice, chronic social defeat stress (CSDS) led to a susceptible or a resilient population, whose proportion was dependent on housing conditions, namely standard housing or enriched environment. Rank-rank-hypergeometric overlap (RRHO), a threshold-free approach that ranks genes by their p value and effect size direction, was used to identify genes from a continuous gradient of significancy that were concordant across groups. In mice treated with CORT and in standard-housed susceptible mice, differentially expressed genes (DEGs) were concordant for gene networks involved in neurotransmission, cytoskeleton function, and vascularization. Weighted gene co-expression analysis generated 54 gene hub modules and revealed two modules in which both CORT and CSDS-induced enrichment in DEGs, whose function was concordant with the RRHO predictions, and correlated with behavioral resilience or susceptibility. These data showed transcriptional concordance across models in which the stress coping depends upon hormonal, environmental, or genetic factors revealing common genomic drivers that embody the multifaceted nature of stress-related disorders.

scholarly journals Synaptonemal Complex Length Variation in Wild-Type Male Mice

Genes ◽  
2010 ◽  
Vol 1 (3) ◽  
pp. 505-520 ◽  
Author(s):  
Neil M. Vranis ◽  
Godfried W. Van der Heijden ◽  
Safia Malki ◽  
Alex Bortvin
Keyword(s):  
Synaptonemal Complex ◽  
Length Variation ◽  
Male Mice ◽  
Wild Type ◽  
Wild Type Male ◽  
Complex Length

scholarly journals Targeted deletion of Atg5 in chondrocytes promotes age-related osteoarthritis

2015 ◽  
Vol 75 (3) ◽  
pp. 627-631 ◽  
Author(s):  
Thibault Bouderlique ◽  
Karuna K Vuppalapati ◽  
Phillip T Newton ◽  
Lei Li ◽  
Björn Barenius ◽  
...  
Keyword(s):  
Cell Death ◽  
Research Society ◽  
Targeted Deletion ◽  
Nucleotidyl Transferase ◽  
Medial Meniscectomy ◽  
Age Related ◽  
Osteoarthritis Research Society ◽  
Post Traumatic ◽  
Safranin O ◽  
And Control

ObjectivesIt has been suggested that the lysosomal recycling process called macro-autophagy plays a role in osteoarthritis development. We thus decided to genetically ablate the autophagy-indispensable Atg5 gene specifically in chondrocytes and analyse the development of osteoarthritis upon aging and in a post-traumatic model.MethodsMice lacking the Atg5 gene in their chondrocytes (Atg5cKO) were generated by crossing Atg5-floxed mice with transgenic mice that expressed cre recombinase driven by the collagen type 2 promoter. Animals were analysed at the age of 2, 6 and 12 months for age-related osteoarthritis or underwent mini-open partial medial meniscectomy at 2 months of age and were analysed 1 or 2 months after surgery. We evaluated osteoarthritis using the Osteoarthritis Research Society International (OARSI) scoring on safranin-O-stained samples. Cell death was evaluated by terminal deoxy-nucleotidyl-transferase-mediated deoxy-UTP nick end labelling (TUNEL) and by immunostaining of cleaved caspases.ResultsWe observed the development of osteoarthritis in Atg5cKO mice with aging including fibrillation and loss of proteoglycans, which was particularly severe in males. The ablation of Atg5 was associated with an increased cell death as assessed by TUNEL, cleaved caspase 3 and cleaved caspase 9. Surprisingly, no difference in the development of post-traumatic osteoarthritis was observed between Atg5cKO and control mice.ConclusionsAutophagy protects from age-related osteoarthritis by facilitating chondrocyte survival.

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