igf 1  (MedChemExpress)

Journal: Bioactive Materials

Article Title: Sulfated polysaccharide prevents senescent adipocyte-driven osteonecrosis by stem cell fate reprogramming

doi: 10.1016/j.bioactmat.2025.11.039

Figure Lengend Snippet: Schematic illustration of the senescence-regulatory mechanisms of the sulfated polysaccharide in the glucocorticoid-induced bone marrow microenvironment. Bone marrow senescence plays a critical role in the pathogenesis of osteonecrosis. Glucocorticoids act on bone marrow target cells—adipocytes—to initiate primary bone marrow senescence via triggering a positive feedback loop through the prostaglandin/PPARγ/INK signaling axis. Subsequently, these senescent adipocytes propagate SASP factors to adjacent healthy cells through paracrine signaling or direct cell–cell contact, leading to secondary senescence. Sulfated chitosan (SCS) reprograms the lineage commitment bias of LepR + MSCs by activating the IGF-1/PI3K/Akt/mTOR signaling cascade, suppressing adipogenic differentiation and lipid biosynthesis pathways. SCS attenuates the spread of primary adipocyte senescence into secondary senescence, limiting the progressive amplification of the senescence cascade. Ultimately, this strategy halts the onset of senescence-driven osteonecrosis at an early stage and preserves the functional stability of the bone marrow microenvironment.

Article Snippet: Furthermore, to explore the molecular mechanisms by which SCS regulates MSCs lineage bias, bone marrow supernatant was collected on day 7 following co-treatment with SCS and MPS, and ELISA assays for IGF-1 (R&D Systems, MG100) and BMP-2 (R&D Systems, DBP200) were performed as described above.

Techniques: Amplification, Functional Assay

Journal: Bioactive Materials

Article Title: Sulfated polysaccharide prevents senescent adipocyte-driven osteonecrosis by stem cell fate reprogramming

doi: 10.1016/j.bioactmat.2025.11.039

Figure Lengend Snippet: SCS modulates mesenchymal stem cell lineage bias via activation of the IGF-1/PI3K/Akt/mTOR signaling pathway. ( A ) Quantitative analysis of osteocyte morphology in the trabecular bone matrix of the bone marrow at week 6 after MPS treatment with or without SCS, in the presence of various neutralizing antibodies (NAbs) and antagonistic proteins. ( B ) ELISA analysis of IGF-1 and BMP-2 levels in the femoral bone marrow and peripheral serum at day 7 following SCS treatment under MPS conditions. ( C and D ) Western blot analysis of phospho-PI3K, phospho-Akt, and phospho-mTOR (C), as well as phospho-Smad1/5/8, phospho-ERK, and phospho-p38 (D), in CD45 − Ter119 − CD31 − LepR + MSCs after 15-min stimulation with conditioned medium (CM) derived from bone marrow fluid at day 7 following SCS treatment. ( E – G ) Representative flow cytometry plots (E, F) and quantitative analysis (G) of CD45 − CD31 − Sca-1 + CD24 − adipocyte progenitor cells (APCs), CD45 − CD31 − Sca-1 + CD24 + MSCs (E), and CD45 − CD31 − Sca-1 − PDGFRα + (Pα + ) osteoprogenitor cells (OPCs) (F) from femoral bone marrow at day 14 post-MPS induction with or without combined treatment using SCS and IGF-1 NAb or Noggin. ( H and I ) Representative SA-β-Gal staining images (green) of the femur (H), and corresponding quantification (I), at week 4 following MPS treatment with SCS in combination with IGF-1 NAb or DMH1. Insets show magnified views of bone marrow (BM) and trabecular bone matrix (TBM) regions. (Scale bars, 100 μm and 25 μm) ( J ) qPCR analysis of 12 senescence-associated markers in ex vivo femoral bone tissues at week 4 following MPS treatment with SCS in combination with IGF-1 NAb or DMH1. ( K ) Representative Oil Red O staining images of CD45 − Ter119 − CD31 − LepR + MSCs sorted from femurs at day 7 following MPS treatment with SCS in combination with LY294002 or LDN-193189, after in vitro adipogenic induction. (Scale bars, 50 μm and 25 μm) ( L and M ) γ-H2A.X and telomere-associated DNA damage foci (TAFs) co-localization analysis (L), and corresponding quantification (M), in CD45 − Ter119 − CD31 + arteriolar ECs sorted from femurs at day 28 following MPS treatment with SCS in combination with rapamycin or LDN-193189, using immuno-FISH staining. (Scale bars, 7 μm and 1 μm) ( N and O ) Sequential fluorescent labeling using calcein (N) and quantification of mineral apposition rate (O) in femurs treated with SCS and MPS for 4 weeks, with or without LY294002 and/or GW9662. (Scale bars, 50 μm) ( P ) ELISA analysis of five senescence-associated cytokines in femoral bone marrow at day 28 following MPS treatment with SCS in combination with rapamycin and/or T0070907. ( Q and R ) Representative t-distributed stochastic neighbor embedding (t-SNE) plots (Q) from flow cytometric analysis of CD45 − CD31 − Sca-1 + CD24 − APCs, CD45 − CD31 − Sca-1 + CD24 + MSCs, CD45 − CD31 − Sca-1 − Pα + OPCs, CD45 − Ter119 − CD31 + arteriolar ECs, and CD45 − Ter119 − Emcn + sinusoidal ECs at day 14 following MPS treatment with SCS in combination with IGF-1 and/or rosiglitazone, and quantitative analysis of APCs (R) ( S ) Heatmap showing the fluorescent intensity distribution of Lamin-B1 expression across five cellular subpopulations as identified in the t-SNE clustering plot. ∗ P < 0.05 vs. IgG (empty lacunae); # P < 0.05 vs. IgG (filled lacunae). ∗ P < 0.05 vs. SCS; # P < 0.05 vs. SCS + IGF-1 NAb. Data are presented as mean ± SD. ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001; ns, not significant. Statistical significance was determined using an unpaired two-tailed Student's t -test ( B ), or one-way ANOVA with Tukey's post hoc test ( A, G, I, J, O, P and R ).

Article Snippet: Furthermore, to explore the molecular mechanisms by which SCS regulates MSCs lineage bias, bone marrow supernatant was collected on day 7 following co-treatment with SCS and MPS, and ELISA assays for IGF-1 (R&D Systems, MG100) and BMP-2 (R&D Systems, DBP200) were performed as described above.

Techniques: Activation Assay, Enzyme-linked Immunosorbent Assay, Western Blot, Derivative Assay, Flow Cytometry, Staining, Ex Vivo, In Vitro, Labeling, Expressing, Two Tailed Test

Journal: Investigative Ophthalmology & Visual Science

Article Title: Rexinoid NEt-3IB Promotes Resident Macrophage Gene Expression and Mitigates Desiccation-Induced Ocular Surface Disease

doi: 10.1167/iovs.67.4.31

Figure Lengend Snippet: Effects of rexinoid treatment on macrophage gene and protein expression in the desiccation stress dry eye model and potential macrophage-derived IGF-1/IGF-1R signaling axis. ( A ) Heatmaps showing z -score–scaled expression of selected latent-time–associated genes in four treatment groups (NS, None [untreated], Veh, and NEt-3IB) in conjunctival monocyte/macrophage lineage cells sorted from CD45⁺ cells after 5 days of desiccating stress (DS5) ( P adj < 0.001). Genes are organized into five functional categories. The color scale represents z -scores of normalized expression ( blue , low; red , high). These data show desiccating stress–associated shifts in macrophage gene programs and their modulation by NEt-3IB, including enrichment of reparative and growth factor–related genes such as Igf1 . Full gene names for the abbreviations are provided in . ( B ) Representative flow cytometry histograms and quantification validating selected macrophage-associated markers in conjunctival immune cells. ( Left ) Representative histograms of CX3CR1 staining with fluorescence-minus-one (FMO) control, with corresponding quantification of the percentage of CD45⁺CD11b⁺CX3CR1⁺ cells. ( Right ) Representative histograms of IGF-1 staining with FMO control, with corresponding quantification of the percentage of CD45⁺CD11b⁺Mrc1⁺IGF-1⁺ cells. Compared with DS5 no treatment and DS5+vehicle controls, DS5+NEt-3IB increased the proportion ofx CX3CR1⁺ and Mrc1⁺IGF-1⁺ myeloid cells. Each dot represents one biological replicate; bars show mean ± SEM. Statistical significance is indicated as shown: ** P < 0.01; **** P < 0.001; **** P < 0.0001; ns, not significant. ( C ) Representative immunofluorescence images showing IGF-1R/WGA/DAPI staining of wholemount conjunctiva showing surface view ( top ) and βIII-tubulin/IGF-1R/DAPI staining in the cornea ( bottom ). IGF-1R localization is shown because IGF-1 is produced by ocular surface resident macrophages, suggesting a potential macrophage-derived IGF-1/IGF-1R signaling axis acting on ocular surface epithelial and neural compartments during DS. Scale bar : 100 µm.

Article Snippet: The following primary antibodies were used: βIII-tubulin (ab215037; Abcam, Cambridge, UK) and human/mouse IGF-1R (AF-305-NA; R&D Systems, Minneapolis, MN, USA).

Techniques: Expressing, Derivative Assay, Functional Assay, Flow Cytometry, Staining, Fluorescence, Control, Immunofluorescence, Produced