Post-menopausal women present with the highest incidence and morbidity of knee osteoarthritis (KOA), but no disease-modifying therapies are available. This treatment gap may be driven by the absence of menopause in preclinical studies, as rodents do not naturally maintain a menopausal phenotype. Here, we employed a chemically-induced menopause model to map the trajectory of KOA at the tissue and proteome levels and test therapeuticsin silico. Middle-aged female mice were randomized to sesame oil (non-menopause) or 4-vinycyclohexene diepoxide (menopause) injections. Following comprehensive validation of our model, knees were collected across perimenopause and menopause for histology, and cartilage samples were micro-dissected for mass spectrometry proteomics. Menopause mice displayed aggravated cartilage degeneration and synovitis relative to non-menopause mice. An unbiased pathway analysis revealed progesterone as a predominant driver of pathological signaling cascades within the cartilage proteome. Network medicine-based analyses suggested that menopause induction amplifies chondrocyte senescence, actin cytoskeleton-based stress, and extracellular matrix disassembly. We then usedin silicodrug testing to evaluate how restoration of sex hormones impacted the cartilage network. The greatest restoration was observed with combined estradiol/progesterone treatment (i.e., hormone therapy), althoughin silicotreatment with a senolytic drug also partially recovered the cartilage proteome. Taken together, our findings using a translatable female aging model demonstrate that menopausal aging induces progressive cartilage degeneration and amplifies age-related synovitis. These changes may be driven by a previously unappreciated role of progesterone loss and menopause-induced cellular senescence. Lastly,in silicotreatment suggests an estradiol/progesterone cocktail or senolytics may attenuate menopause-induced cartilage pathology.One Sentence SummaryMenopause induces cartilage degradation, senescence, and extracellular matrix disassembly, while hormone therapy restores the cartilage proteome.

Although magnetic field exposure is a well-established diagnostic tool, its use as a therapeutic in regenerative medicine is relatively new. Our goal here was to evaluate how magnetic fields affect neural repair in vitro by performing a systematic review of the literature, mathematical modeling, and meta-analyses. The 38 included articles presented with high heterogeneity, representing 13 cell types, magnitudes ranging from 0.0002-10,000 mT, frequencies from 0-150 Hz, and exposure times lasting from one hour to several weeks. Mathematical modeling revealed that increasing magnetic field magnitude increases neural progenitor cell (NPC) viability. For regenerative processes that were not influenced by magnitude, frequency, and time, we integrated data with meta-analyses. Results revealed that magnetic field exposure increases NPC proliferation while decreasing astrocytic differentiation. Collectively, our work identifies neural repair processes that may be most responsive to magnetic field exposure and provides a framework for novel hypothesis and technology development.