Comparison of joint degeneration and pain in male and female mice in DMM model of osteoarthritis

Hwang, Hyun Sook; Park, In Young; Hong, Jeong-Im; Kim, Ju‐Ryoung; Kim, Hyun Ah

doi:10.1016/j.joca.2021.02.007

Cited by 49 publications

(40 citation statements)

References 46 publications

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“…Altered growth rate and mechanical modulation of GP function appear to result from complex interactions of changes in the states of these chondrocytes, as does the rate of GP closure due to the formation of bone bridges forming and spanning the width of the GP. Therefore, the differences between our results and those seen by Lamuedra et al., could be due to the different ages examined, or due to the different sexes of the animals as it is known that DMM in female mice results in less severe articular cartilage damage compared to male mice ( 27 ).…”

Section: Discussioncontrasting

confidence: 85%

Characterisation of Growth Plate Dynamics in Murine Models of Osteoarthritis

et al. 2021

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The purpose of this study was to investigate growth plate dynamics in surgical and loading murine models of osteoarthritis, to understand whether abnormalities in these dynamics are associated with osteoarthritis development. 8-week-old C57BL/6 male mice underwent destabilisation of medial meniscus (DMM) (n = 8) surgery in right knee joints. Contralateral left knee joints had no intervention (controls). In 16-week-old C57BL/6 male mice (n = 6), osteoarthritis was induced using non-invasive mechanical loading of right knee joints with peak force of 11N. Non-loaded left knee joints were internal controls. Chondrocyte transiency in tibial articular cartilage and growth plate was confirmed by histology and immunohistochemistry. Tibial subchondral bone parameters were measured using microCT and correlated to 3-dimensional (3D) growth plate bridging analysis. Higher expression of chondrocyte hypertrophy markers; Col10a1 and MMP13 were observed in tibial articular cartilage chondrocytes of DMM and loaded mice. In tibial growth plate, Col10a1 and MMP13 expressions were widely expressed in a significantly enlarged zone of proliferative and hypertrophic chondrocytes in DMM (p=0.002 and p<0.0001, respectively) and loaded (both p<0.0001) tibiae of mice compared to their controls. 3D quantification revealed enriched growth plate bridging and higher bridge densities in medial compared to lateral tibiae of DMM and loaded knee joints of the mice. Growth plate dynamics were associated with increased subchondral bone volume fraction (BV/TV; %) in medial tibiae of DMM and loaded knee joints and epiphyseal trabecular bone volume fraction in medial tibiae of loaded knee joints. The results confirm articular cartilage chondrocyte transiency in a surgical and loaded murine models of osteoarthritis. Herein, we reveal spatial variation of growth plate bridging in surgical and loaded osteoarthritis models and how these may contribute to anatomical variation in vulnerability of osteoarthritis development.

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Section: Discussioncontrasting

confidence: 85%

Characterisation of Growth Plate Dynamics in Murine Models of Osteoarthritis

et al. 2021

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“…Starting from preclinical studies, several authors, and more recently a systematic review, highlighted some important differences in OA between male and female subjects [ 25 , 26 , 27 ]. For in vitro studies, sex differences emerged at the molecular level and in the gene expression of inflammatory cytokines and hormone receptors.…”

Section: Introductionmentioning

confidence: 99%

Gender and Sex Are Key Determinants in Osteoarthritis Not Only Confounding Variables. A Systematic Review of Clinical Data

Tschon

Contartese

Pagani

et al. 2021

JCM

138

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Many risk factors for osteoarthritis (OA) have been noted, while gender/sex differences have been understated. The work aimed to systematically review literature investigating as primary aim the relationship between gender/sex related discriminants and OA. The search was performed in PubMed, Science Direct and Web of Knowledge in the last 10 years. Inclusion criteria were limited to clinical studies of patients affected by OA in any joints, analyzing as primary aim gender/sex differences. Exclusion criteria were review articles, in vitro, in vivo and ex vivo studies, case series studies and papers in which gender/sex differences were adjusted as confounding variable. Of the 120 records screened, 42 studies were included. Different clinical outcomes were analyzed: morphometric differences, followed by kinematics, pain, functional outcomes after arthroplasty and health care needs of patients. Women appear to use more health care, have higher OA prevalence, clinical pain and inflammation, decreased cartilage volume, physical difficulty, and smaller joint parameters and dimensions, as compared to men. No in-depth studies or mechanistic studies analyzing biomarker differential expressions, molecular pathways and omic profiles were found that might drive preclinical and clinical research towards sex-/gender-oriented protocols.

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“…In relation to mechanobiology of the meniscus, we investigated the transcriptome profile changes of various mechanosensitive molecules such as TRPV1/4 , PIEZO1 , TMEM63A/B/C , and RUNX2 ( McNulty and Guilak, 2015 ; Servin-Vences et al, 2017 ; Agarwal et al, 2021 ; Hwang et al, 2021 ; Lee et al, 2021 ). Furthermore, the mechanotransduction function of FOSB in MFCs ( Szojka et al, 2021a ) was reported by Szojka et al, and its function in the IL-17 signalling pathway was well demonstrated ( Benderdour et al, 2002 ).…”

Section: Resultsmentioning

confidence: 99%

Engineered Human Meniscus in Modeling Sex Differences of Knee Osteoarthritis in Vitro

Kunze

et al. 2022

Front. Bioeng. Biotechnol.

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Background: Osteoarthritis (OA) primarily affects mechanical load-bearing joints. The knee joint is the most impacted by OA. Knee OA (KOA) occurs in almost all demographic groups, but the prevalence and severity are disproportionately higher in females. The molecular mechanism underlying the pathogenesis and progression of KOA is unknown. The molecular basis of biological sex matters of KOA is not fully understood. Mechanical stimulation plays a vital role in modulating OA-related responses of load-bearing tissues. Mechanical unloading by simulated microgravity (SMG) induced OA-like gene expression in engineered cartilage, while mechanical loading by cyclic hydrostatic pressure (CHP), on the other hand, exerted a pro-chondrogenic effect. This study aimed to evaluate the effects of mechanical loading and unloading via CHP and SMG, respectively, on the OA-related profile changes of engineered meniscus tissues and explore biological sex-related differences.Methods: Tissue-engineered menisci were made from female and male meniscus fibrochondrocytes (MFCs) under static conditions of normal gravity in chondrogenic media and subjected to SMG and CHP culture. Constructs were assayed via histology, immunofluorescence, GAG/DNA assays, RNA sequencing, and testing of mechanical properties.Results: The mRNA expression of ACAN and COL2A1, was upregulated by CHP but downregulated by SMG. COL10A1, a marker for chondrocyte hypertrophy, was downregulated by CHP compared to SMG. Furthermore, CHP increased GAG/DNA levels and wet weight in both female and male donors, but only significantly in females. From the transcriptomics, CHP and SMG significantly modulated genes related to the ossification, regulation of ossification, extracellular matrix, and angiogenesis Gene Ontology (GO) terms. A clear difference in fold-change magnitude and direction was seen between the two treatments for many of the genes. Furthermore, differences in fold-change magnitudes were seen between male and female donors within each treatment. SMG and CHP also significantly modulated genes in OA-related KEGG pathways, such as mineral absorption, Wnt signalling pathway, and HIF-1 signalling pathway.Conclusion: Engineered menisci responded to CHP and SMG in a sex-dependent manner. SMG may induce an OA-like profile, while CHP promotes chondrogenesis. The combination of SMG and CHP could serve as a model to study the early molecular events of KOA and potential drug-targetable pathways.

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Comparison of joint degeneration and pain in male and female mice in DMM model of osteoarthritis

Cited by 49 publications

References 46 publications

Characterisation of Growth Plate Dynamics in Murine Models of Osteoarthritis

Characterisation of Growth Plate Dynamics in Murine Models of Osteoarthritis

Gender and Sex Are Key Determinants in Osteoarthritis Not Only Confounding Variables. A Systematic Review of Clinical Data

Engineered Human Meniscus in Modeling Sex Differences of Knee Osteoarthritis in Vitro

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