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A network medicine approach to elucidate mechanisms underlying menopause-induced knee osteoarthritis

ABSTRACT: This study was aimed at understanding the effects of menopause on knee osteoarthritis, specifically the cartilage proteome. Middle-aged female mice were randomized to receive intraperitoneal injections of either 4-vinylcyclohexene diepoxide (VCD) or sesame oil for 10 consecutive days. Through a serious of validation experiments, we and others have shown that VCD induces a menopausal phenotype, as evidenced by loss of estrus cyclicity and modification to sex hormone profiles. We also showed in our work that VCD injected mice present with more severe cartilage degeneration than sesame oil injected mice. Knee cartilage from the tibial plateau and femoral condyles were microdissected at mid-perimenopause (75 days after the first injection), start of menopause (115 days after the first injection), and late menopause (195 days after the first injection). These times points were chosen since cartilage pathology first presented in the VCD group, but not the sesame oil group, at the start of menopause. Cartilage samples were lyophilized and mass spectrometry proteomics were performed.

INSTRUMENT(S): timsTOF Pro, Q Exactive Plus

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Fabrisia Ambrosio

PROVIDER: MSV000092077 | MassIVE | Thu Jun 01 08:56:00 BST 2023

SECONDARY ACCESSION(S): PXD042619

REPOSITORIES: MassIVE

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Project description:Methods: During the last trimester of the gestation, 12 heifers were immunized using intramuscular injection with heat-killed E. coli P4 emulsified in Montanide ISA 61VG® oil adjuvant (SEPPIC), as recommended by the manufacturer. Two months later, half of the heifers (IM group, n=6) got a second injection as a booster. Others received 50 µg of protein concentrate prepared from E. coli P4 supernate in two quarters (IMM group, n=6). Cows of the control group (CONT, n=6) were injected intramuscularly with adjuvant only at the same dates. Cows were then challenged on average at 49 days in milk in one healthy quarter by infusion of a E. coli P4 bacterial suspension (10e3 bacteria). Blood was collected before experiment, and seven days after the first and the second injection (immunization phase), and then at 0, 12 and 40 hours after infection (challenge phase). Results : Whole blood transcriptome through RNA-seq identifies the main biological functions altered during an E. coli mastitis. Systemic and mammary routes of E. coli immunization elicit different gene expression profiles that correlated with the levels of protection Conclusions: Intramuscular immunization is correlated with a high systemic Th1 response that is not as protective as the local route of immunization. During the last trimester of the gestation, 12 heifers were immunized using intramuscular injection with heat-killed E. coli P4 emulsified in Montanide ISA 61VG® oil adjuvant (SEPPIC), as recommended by the manufacturer. Two months later, half of the heifers (IM group, n=6) got a second injection as a booster. Others received 50 µg of protein concentrate prepared from E. coli P4 supernate in two quarters (IMM group, n=6). Cows of the control group (CONT, n=6) were injected intramuscularly with adjuvant only at the same dates. Cows were then challenged on average at 49 days in milk in one healthy quarter by infusion of a E. coli P4 bacterial suspension (10e3 bacteria). Blood was collected before experiment, and seven days after the first and the second injection (immunization phase), and then at 0, 12 and 40 hours after infection (challenge phase).

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A network medicine approach to elucidate mechanisms underlying menopause-induced knee osteoarthritis

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