Alzheimer’s Disease (AD) is characterized by cognitive impairment and the presence of amyloid-β (Aβ) plaques and tau tangles. This study was conducted to assess the effects of white button mushroom (WBM) supplementation on spatial memory and plaque formation in mice with mutations in amyloid (Aβ). Mice with amyloid precursor protein (hAPP) mutations and their wildtype (WT) littermates were fed a 10% white button mushroom (WBM) feed ad libitum three times per week, in addition to their normal diet. Morris water maze (MWM) was conducted at 14 and 32 weeks of age to assess spatial memory and Aβ plaque pathology in the hippocampus was analyzed. Our results showed that hAPP mice on the WBM diet were faster in reaching the platform in the MWM compared to hAPP mice on the control diet at 32 weeks (p < 0.05). Significantly fewer plaque deposits were found in the hippocampi of hAPP mice on the WBM diet compared to those on the control diet at 32 weeks (p < 0.05). Overall, hAPP mice on the WBM diet had improved spatial memory at 32 weeks of age compared to those on the control diet and exhibited fewer amyloid plaques.

To investigate the effects of a matrikine, fibronectin fragment (FN7-10), on human osteoarthritic (OA) synovial fibroblasts and implications for inflammation and cartilage degradation. Joint tissue was obtained from 50 OA patients undergoing knee arthroplasty. Isolated synovial fibroblasts were treated with 1 µM of FN7-10 or PBS as control. Cytokine protein arrays were used to identify differentially secreted inflammatory mediators in conditioned media (CM). Bulk RNA-seq was used to evaluate transcriptional changes. Monocytic THP-1 cells in transwell assays were used to evaluate chemotactic activity of CM. Macrophage differentiation of THP-1 cells was assessed via qPCR and flow cytometry. Chondrocyte gene expression was evaluated by qPCR and glycosaminoglycan (GAG) production by Alcian blue assays. FN7-10 stimulation of synovial fibroblasts induced an inflammatory secretome, including production of chemokines. RNA-seq analysis confirmed FN7-10 induced upregulation of chemokines, including CCL5, CCL7, CCL8, CCL20, CXCL5 and CXCL10, which displayed mean transcriptional log-2-fold changes of 3.89 (CI, 2.81 - 4.97). CM from FN7-10-stimulated synovial fibroblasts increased THP-1 chemotaxis by 7.8-fold (CI, 3.26 - 12.35) which was reduced by CCR2 or CXCR2 inhibitors and promoted monocyte to macrophage differentiation characterized by an increase in pro-inflammatory gene expression and CD14. Chondrocytes treated with FN7-10 synovial fibroblast CM showed elevated IL6 and MMP1 and decreased ACAN and COL2A1 expression, along with reduced GAG levels. The matrikine FN7-10 promotes an inflammatory synovial fibroblast phenotype. Proinflammatory mediators, including chemokines, released from activated synovial fibroblasts recruit monocytes that may exacerbate joint inflammation and can also promote increased catabolic activity in chondrocytes.

Objective: To determine how fibronectin fragment (Fn-f), a matrikine that induces an osteoarthritis (OA)-like phenotype, reshapes chondrocyte states and transcriptional programs at single-cell resolution. Design: Primary human ankle chondrocytes from two cadaveric donors without OA were treated with PBS or purified recombinant Fn-f for 18 hours and profiled by single-cell RNA sequencing. Transcriptional states were characterized by marker genes and functional enrichment, compared with classifications used for OA chondrocytes, and evaluated for Fn-f-dependent changes in abundance and transcriptional programs. Results: Five transcriptionally distinct populations were identified with features that matched previous classifications of effector, inflammatory, pre-hypertrophic/fibrochondrocyte, reparative, and homeostatic chondrocytes. Fn-f markedly redistributed cells among these states, enriching inflammatory chondrocytes while reducing effector and reparative populations. Within transcriptional states, Fn-f differentially altered matrix/cartilage, inflammatory, and stress/immediate-early programs. These responses did not uniformly correspond to assigned subtype identities, demonstrating that transcriptional programs can be dynamically deployed across chondrocyte states. Conclusions: Controlled perturbations of healthy chondrocytes complement observational OA atlases by resolving stimulus-dependent changes in chondrocyte state abundance and transcriptional programs. Discordance between subtype annotations and dynamic functional programs further highlights the need for harmonized definitions of chondrocytes across phenotypic states.