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: Continuous intraosseous administration of SCS prevents glucocorticoid-induced bone degeneration. ( A ) Schematic illustration of the glucocorticoid (GC; MPS)-induced bone deterioration and intraosseous SCS treatment. ( B-D ) Representative H&E staining images of the femur at 6 weeks (B). Magnified views of the cortical bone and trabecular bone in the marrow cavity are shown on the right. Solid arrows indicate normal osteocytes, while hollow arrows indicate empty osteocyte lacunae. Quantification of empty lacunae ratios in cortical bone (C) and trabecular bone (D). n = 6 biological replicates. (Scale bars, 500 μm and 25 μm) ( E-H ) Representative immunofluorescence staining of OPN + mature osteoblasts, osteolectin + osteoprogenitors, and VE-cadherin + endothelial cells (ECs) in femur at 6 weeks (E), and corresponding quantifications (F–H). n = 6 biological replicates. (Scale bars, 100 μm and 20 μm) ( I and J ) Representative flow cytometry plots of capillary subtypes in the femur (I), with quantification of CD45 − Ter119 − CD31 hi Emcn hi ECs (J). n = 6 biological replicates. ( K and L ) Flow cytometry plots showing Sca-1 hi CD31 hi arteriolar ECs (K), and corresponding quantification (L). n = 6 biological replicates. ( M and N ) Representative micro-CT 3D images of the femur (M). Quantitative analysis of percent bone volume (BV/TV) (N). n = 6 biological replicates. (Scale bars, 1.5 mm, 600 μm and 545 μm) ( O and P ) ELISA analysis of VEGF (O) and PDGF-BB (P) levels in bone marrow supernatant and peripheral serum from PBS- and SCS-treated groups at week 6. n = 6 biological replicates. ( Q ) ELISA quantification of the osteogenic factor osteocalcin in peripheral serum at week 6. n = 6 biological replicates. 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 one-way ANOVA with Tukey's post hoc test ( C, D, F, G, H, J, L, N, O, P and Q ).

Article Snippet: Serum concentrations of the osteogenic marker osteocalcin (NOVUS, NBP2-68151) were also measured.

Techniques: Staining, Immunofluorescence, Flow Cytometry, Micro-CT, Enzyme-linked Immunosorbent 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 targets downstream senescent lineage commitment of bone marrow MSCs to mitigate GC-induced bone deterioration. ( A ) Schematic diagram illustrating the experimental design: CD45 − Ter119 − CD31 − LepR + MSCs isolated from mice co-treated with SCS and MPS for 7 days were subjected to in vitro lineage-competitive differentiation, followed by DEX-induced senescence in lineage-mixed cells. These cells were then adoptively transplanted into healthy bone marrow cavity to assess bone deterioration development. ( B ) Representative H&E-stained images of the femur 12 weeks after adoptive transfer. PBS-DEX group: LepR + MSCs from PBS and MPS co-treated mice subjected to in vitro lineage differentiation and DEX-induced senescence, followed by transplantation. SCS-DEX group: LepR + MSCs from SCS and MPS co-treated mice processed similarly. PBS group: solvent control without cell transplantation. Solid arrows indicate intact osteocytes; hollow arrows indicate empty lacunae. (Scale bars, 250 μm and 25 μm) ( C – E ) Quantitative analysis of marrow hypertrophic adipocyte diameter (C), proportion of empty osteocyte lacunae in trabecular bone (D), and adipocyte number (E) in the metaphysis 12 weeks post-transplantation. n = 19 biological replicates (C), n = 6 biological replicates (D), n = 8 biological replicates (E). ( F ) Quantification of empty lacunae in epiphysis at 12 weeks post-transplantation. n = 6 biological replicates. ( G – I ) Representative flow cytometry plots of capillary ECs subtypes in the femur at 12 weeks (G), with quantification of CD45 − Ter119 − CD31 hi Emcn hi ECs (H) and CD45 − Ter119 − CD31 lo Emcn lo ECs (I). n = 6 biological replicates. ( J and K ) Representative flow cytometry plots (J) and corresponding quantification (K) of CD45 − Ter119 − Sca-1 hi CD31 hi arteriolar ECs in the femur at 12 weeks post-transplantation. n = 6 biological replicates. ( L ) Representative micro-CT images of the femur at 12 weeks post-transplantation across different treatment groups. (Scale bars, 1.5 mm and 500 μm) ( M – P ) Quantitative analysis of bone parameters in the metaphysis: bone mineral density (BMD) (M), percent bone volume (BV/TV) (N), trabecular separation (Tb.Sp) (O), and trabecular number (Tb.N) (P). n = 6 biological replicates. ( Q ) Serum ELISA analysis of the osteogenic marker osteocalcin at 12 weeks post-transplantation. n = 6 biological replicates. ( R and S ) ELISA analysis of PDGF-BB (R) and VEGF (S) in both bone marrow supernatant and peripheral serum at 12 weeks post-transplantation. n = 6 biological replicates. 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 one-way ANOVA with Tukey's post hoc test ( C, D, E, F, H, I, K, M, N, O, P, Q, R and S ).

Article Snippet: Serum concentrations of the osteogenic marker osteocalcin (NOVUS, NBP2-68151) were also measured.

Techniques: Isolation, In Vitro, Staining, Adoptive Transfer Assay, Transplantation Assay, Solvent, Control, Flow Cytometry, Micro-CT, Enzyme-linked Immunosorbent Assay, Marker

Journal: Bone Reports

Article Title: Uncoupled bone remodeling drives myeloma bone disease in Vk*MYC mouse model of multiple myeloma

doi: 10.1016/j.bonr.2026.101910

Figure Lengend Snippet: Implantation of Vk*MYC cells leads to development of MM and MMBD in recipient mice. 3D reconstruction image of femur made in Drishti Visualization Software from control (naïve) mice or mice injected with Vk*MYC cells, 8–9 weeks after inoculation. Vk*MYC mice develop lesions (black arrows) (A). Quantitation of number of lesions (B) and area of lesions (C) in mice, 8–9 weeks after intravenous injection of 250,000 Vk*MYC cells in 200 μL PBS via the tail vein. ELISA of bone turnover markers and CTX-1 (D), P1NP (E) in serum from control (naïve) mice or mice injected with Vk*MYC cells, 8–9 weeks after inoculation. Data represent mean ± S.E.M, * P ≤ 0.05, ** P ≤ 0.01, *** P ≤ 0.001, **** P ≤ 0.0001, two tailed unpaired Student t -test.

Article Snippet: Serum concentrations of the bone formation marker amino terminal propeptide of type I procollagen (P1NP) and the bone resorption marker C-telopeptide of type I collagen (CTX-1) were determined using colorimetric ELISA kits (Immunodiagnostic Systems), following the manufacturer's instructions.

Techniques: Software, Control, Injection, Quantitation Assay, Enzyme-linked Immunosorbent Assay, Two Tailed Test

Journal: European Journal of Clinical Investigation

Article Title: FNDC4 and FNDC5 Attenuate SARS‐CoV‐2 S1‐Induced Inflammatory Responses in Human Adipose Tissue

doi: 10.1111/eci.70215

Figure Lengend Snippet: Effect of FNDC4 and FNDC5 on SARS‐CoV‐2 spike protein S1 subunit‐mediated macrophage M1 polarisation and crosstalk with adipocytes. Effect of co‐incubation of SARS‐CoV‐2 spike protein S1 subunit (100 ng/mL) with FNDC4 (10 ng/mL) or FNDC5 (10 ng/mL) on gene expression of several factors involved in the polarisation of human THP‐1 macrophages toward M1 ( NOS2 ) or M2 ( ARG1 ) phenotypes. as well as in the production of inflammatory ( IL1B ) and anti‐inflammatory ( IL10 ) cytokines in the absence (A) or presence (B) of adipocyte‐conditioned medium (ACM 40%) derived from adipocyte cultures from patients with obesity ( n = 10 per group). Gene expression in unstimulated THP‐1 M0 macrophages was assumed to be 1. (C) HMGB1 release to the culture media in macrophages exposed to ACM 40% in the presence of S1 subunit with FNDC4 or FNDC5. Statistical differences were analysed by two‐way ANOVA followed by a post hoc Tukey's test. a p < 0.05 effect of the SARS‐CoV‐2 S1 subunit; b p < 0.05 effect of treatment with FNDC4 or FNDC5.

Article Snippet: The concentrations of HMGB1 (NBP2‐62766, Novus Biologicals, Cambridge, UK) released to the MCM were assessed by commercially available ELISA kits according to the manufacturer's protocols.

Techniques: Incubation, Gene Expression, Derivative Assay

Journal: European Journal of Clinical Investigation

Article Title: FNDC4 and FNDC5 Attenuate SARS‐CoV‐2 S1‐Induced Inflammatory Responses in Human Adipose Tissue

doi: 10.1111/eci.70215

Figure Lengend Snippet: SARS‐CoV‐2 spike protein S1 subunit promotes a proinflammatory phenotype in visceral adipocytes. (A) Effect of co‐incubation of SARS‐CoV‐2 spike protein S1 subunit (100 ng/mL) with FNDC4 (10 ng/mL) or FNDC5 (10 ng/mL) on protein expression of adiponectin and HMGB1 expression in human visceral adipocytes ( n = 6 per group). (B) HMGB1 gene expression in FNDC4 ‐ and FNDC5 ‐knockdown adipocytes ( n = 8 per group). Statistical differences were analysed by two‐way ANOVA or one‐way followed by a post hoc Tukey's test in case of interaction. * p < 0.05 versus unstimulated or siRNA control cells; † p < 0.05 versus SARS‐CoV‐2 S1‐treated cells.

Article Snippet: The concentrations of HMGB1 (NBP2‐62766, Novus Biologicals, Cambridge, UK) released to the MCM were assessed by commercially available ELISA kits according to the manufacturer's protocols.

Techniques: Incubation, Expressing, Gene Expression, Knockdown, Control