Journal: Nature Communications

Article Title: Thromboxane A2 receptor signalling amplifies osteoclastogenesis in rheumatoid arthritis through ACSL1 associated mitochondrial oxidative metabolism

doi: 10.1038/s41467-026-78259-5

Figure Lengend Snippet: a GO enrichment by GSEA of bulk RNA-seq data from BMMs after 4 days under Ctrl, R, R + STD or R + SQ conditions. GSEA of osteoclast differentiation in R versus Ctrl ( b ), R + STD versus R ( c ) and R + SQ versus R ( d ). PGC-1β/PPARγ ( e , f ) and ACSL1 ( g , h ) protein expression in Ctrl, R, R + STD and R + SQ ( e , g ), or in si-NC- or si- Tbxa2r -transfected BMMs under R or R + U ( f , h ); β-actin, loading control ( n = 5). i Acetyl-CoA levels in Ctrl, R, R + STD and R + SQ ( n = 6). j OCR, maximal respiration and spare respiratory capacity in Ctrl, R, R + TC 1 μM and R + TC 2 μM ( n = 5); Oligo, FCCP and Rot/AA injected as indicated. k TRAP staining and osteoclast-area quantification in Ctrl, R and R + TC ( n = 6). Scale bar, 100 μm. l Model of TBXA2R-regulated osteoclast differentiation and mitochondrial metabolism, assembled using licensed Figdraw elements ( www.figdraw.com ; export ID: YRASTb1819). For a – d , n = 5 for Ctrl and n = 6 per group for R, R + STD and R + SQ. For a – k , n denotes biologically independent experiments. For i – k , data are mean ± SEM and analysed by one-way ANOVA followed by Dunnett’s multiple-comparisons test, with R as reference. Exact P values are shown where possible; values < 0.0001 are reported as such, with full-precision P values and statistical details in the Source Data file. GO Gene Ontology, GSEA gene set enrichment analysis, NES normalized enrichment score, TBXA2R thromboxane A2 receptor, PPARγ peroxisome proliferator-activated receptor γ, PGC-1β PPARγ coactivator 1β, ACSL1 acyl-CoA synthetase long-chain family member 1, BMMs bone marrow-derived macrophages, Ctrl control, R RANKL, STD seratrodast, SQ SQ29548, U U46619, TC triacsin C, si-NC non-targeting control siRNA, si- Tbxa2r Tbxa2r -targeting siRNA, OCR oxygen consumption rate, Oligo oligomycin, FCCP carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, Rot/AA rotenone/antimycin A, TRAP tartrate-resistant acid phosphatase, RANK receptor activator of nuclear factor-κB, RANKL RANK ligand, TXA2 thromboxane A2, FAO fatty acid oxidation, OXPHOS oxidative phosphorylation, TCA tricarboxylic acid, CoA coenzyme A, SEM standard error of the mean. Source data are provided as a Source Data file.

Article Snippet: Immunohistochemical (IHC) staining was used to assess the expression of PGC-1β (Bioss, 1:100, Cat. # bs-7534R), PPARγ (Servicebio, 1:600, Cat. # GB112205 ), and ACSL1 (Proteintech, 1:200, Cat. # 13989-1-AP) in ankle joints.

Techniques: RNA Sequencing, Expressing, Transfection, Control, Injection, Staining, Analysis, Derivative Assay, Phospho-proteomics, Cell Differentiation

Journal: Nature Communications

Article Title: Thromboxane A2 receptor signalling amplifies osteoclastogenesis in rheumatoid arthritis through ACSL1 associated mitochondrial oxidative metabolism

doi: 10.1038/s41467-026-78259-5

Figure Lengend Snippet: a Schematic of CIA induction and treatment in male DBA/1J mice, assembled using a licensed Figdraw mouse illustration ( www.figdraw.com ; export ID: ISWRSfdd0d). Mice were immunized on Day 0, boosted on Day 21, treated intraperitoneally with STD or SQ from Day 28 and sacrificed on Day 56. b Representative H&E and TRAP staining of ankle joints and quantification of pathological scores and TRAP-positive osteoclast numbers in the indicated groups ( n = 10). Scale bars, 100 μm. c Representative μCT images of ankle joints from the indicated groups ( n = 10). d Quantitative μCT analysis of bone parameters, including BV/TV, BS/BV, SMI and BMD ( n = 10). e Representative IHC staining and quantification of positive areas for PGC-1β, PPARγ and ACSL1 in ankle joints ( n = 8). Scale bars, 100 μm. For b – e , n denotes biologically independent mice. Quantitative data are presented as mean ± SEM and were analysed by one-way ANOVA followed by Dunnett’s multiple-comparisons test, with the CIA group as the reference. Exact P values are shown where possible; values < 0.0001 are reported as such, with full-precision P values and statistical details in the Source Data file. TBXA2R thromboxane A2 receptor, CIA collagen-induced arthritis, Ctrl control, STD seratrodast, SQ SQ29548, STD-20 and STD-30 seratrodast at 20 and 30 mg/kg, respectively; SQ-1 and SQ-4 SQ29548 at 1 and 4 mg/kg, respectively, i.p. intraperitoneal, H&E haematoxylin and eosin, TRAP tartrate-resistant acid phosphatase, μCT micro-computed tomography, BV/TV bone volume/total volume, BS/BV bone surface/bone volume, SMI structural model index, BMD bone mineral density, IHC immunohistochemistry, PPARγ peroxisome proliferator-activated receptor γ, PGC-1β PPARγ coactivator 1β, ACSL1 acyl-CoA synthetase long-chain family member 1, SEM standard error of the mean. Source data are provided as a Source Data file.

Article Snippet: Immunohistochemical (IHC) staining was used to assess the expression of PGC-1β (Bioss, 1:100, Cat. # bs-7534R), PPARγ (Servicebio, 1:600, Cat. # GB112205 ), and ACSL1 (Proteintech, 1:200, Cat. # 13989-1-AP) in ankle joints.

Techniques: Staining, Analysis, Immunohistochemistry, Control, Micro-CT

Journal: Nature Communications

Article Title: Thromboxane A2 receptor signalling amplifies osteoclastogenesis in rheumatoid arthritis through ACSL1 associated mitochondrial oxidative metabolism

doi: 10.1038/s41467-026-78259-5

Figure Lengend Snippet: a Schematic of CIA induction in wild-type (WT) and TBXA2R-KO DBA/1J mice, assembled using a licensed Figdraw mouse illustration ( www.figdraw.com ; export ID: ISWRSfdd0d). Mice were immunized on Day 0, boosted on Day 21 and sacrificed on Day 49. b Representative H&E and TRAP staining of ankle joints and quantification of pathological scores and TRAP-positive osteoclast numbers in Ctrl and CIA groups of WT and TBXA2R-KO mice. Scale bars, 100 µm. c Representative μCT images of ankle joints from the indicated groups. d Quantitative μCT analysis of bone parameters, including BV/TV, BS/BV, BMD, BMC and TMD. e Representative IHC staining and quantification of positive areas for PGC-1β, PPARγ and ACSL1 in ankle joints. Scale bars, 100 µm. For b – e , group sizes were WT-Ctrl, n = 4 mice; WT-CIA, n = 4 mice; TBXA2R-KO-Ctrl, n = 3 mice; and TBXA2R-KO-CIA, n = 4 mice. Here, n represents biologically independent mice. Quantitative data are presented as mean ± SEM. Statistical significance was assessed using one-way ANOVA followed by Tukey’s multiple-comparisons test. Exact P values are shown where possible; values < 0.0001 are reported as such, with full-precision P values and statistical details in the Source Data file. TBXA2R thromboxane A2 receptor, TBXA2R-KO germline Tbxa2r knockout, WT wild type, CIA collagen-induced arthritis, Ctrl control, H&E haematoxylin and eosin, TRAP tartrate-resistant acid phosphatase, μCT micro-computed tomography, BV/TV bone volume/total volume, BS/BV bone surface/bone volume, BMD bone mineral density, BMC bone mineral content, TMD tissue mineral density, IHC immunohistochemistry, PPARγ peroxisome proliferator-activated receptor γ, PGC-1β PPARγ coactivator 1β, ACSL1 acyl-CoA synthetase long-chain family member 1, SEM standard error of the mean. Source data are provided as a Source Data file.

Article Snippet: Immunohistochemical (IHC) staining was used to assess the expression of PGC-1β (Bioss, 1:100, Cat. # bs-7534R), PPARγ (Servicebio, 1:600, Cat. # GB112205 ), and ACSL1 (Proteintech, 1:200, Cat. # 13989-1-AP) in ankle joints.

Techniques: Staining, Analysis, Immunohistochemistry, Knock-Out, Control, Micro-CT, Tissue

Journal: Frontiers in Cell and Developmental Biology

Article Title: Lactate promotes mitochondrial biogenesis and fusion via GPR81 to enhance synaptic plasticity-related protein expression in hippocampal cells

doi: 10.3389/fcell.2026.1929409

Figure Lengend Snippet: Primer sequences for RT-qPCR analysis.

Article Snippet: PGC-1α inhibitor SR-18292 (Selleck, S8528) or mitochondrial fusion inhibitor MF18 (Med Chem Express, HY-150031) was applied 30 min before L-lactate/3OBA.

Techniques: Analysis, Sequencing

Journal: Frontiers in Cell and Developmental Biology

Article Title: Lactate promotes mitochondrial biogenesis and fusion via GPR81 to enhance synaptic plasticity-related protein expression in hippocampal cells

doi: 10.3389/fcell.2026.1929409

Figure Lengend Snippet: Modulation of mitochondrial biogenesis and fusion protein expression by L-lactate and GPR81 agonist in primary hippocampal cells. (a) Exemplary immunoblotting analysis (b-h) Bar graphs depict the quantified protein levels (normalized to CON) for PGC-1α, NRF1, NRF2, TFAM, OPA1, MFN1, and MFN2, derived from three independent replicates. Data are expressed as mean ± SD. Statistical significance: * p < 0.05, ** p < 0.01 versus the CON group; n. s., not significant.

Article Snippet: PGC-1α inhibitor SR-18292 (Selleck, S8528) or mitochondrial fusion inhibitor MF18 (Med Chem Express, HY-150031) was applied 30 min before L-lactate/3OBA.

Techniques: Expressing, Western Blot, Analysis, Derivative Assay

Journal: Frontiers in Cell and Developmental Biology

Article Title: Lactate promotes mitochondrial biogenesis and fusion via GPR81 to enhance synaptic plasticity-related protein expression in hippocampal cells

doi: 10.3389/fcell.2026.1929409

Figure Lengend Snippet: The suppressive effect of SR-18292 on genes and proteins regulating mitochondrial biogenesis. (a-c) Quantitative analysis (qRT-PCR) of PGC-1α , NRF1 , and TFAM transcript levels, derived from three independent replicates. (d) Exemplary Western blot image. (e-h) Bar graphs depict the quantified protein levels for PGC-1α, NRF1, NRF2, and TFAM, derived from six independent replicates. Data are expressed as mean ± SD. Statistical significance: * p < 0.05, ** p < 0.01, *** p < 0.001 versus the LA group. # p < 0.05, ## p < 0.01, ### p < 0.001 versus the 3OBA group.

Article Snippet: PGC-1α inhibitor SR-18292 (Selleck, S8528) or mitochondrial fusion inhibitor MF18 (Med Chem Express, HY-150031) was applied 30 min before L-lactate/3OBA.

Techniques: Analysis, Quantitative RT-PCR, Derivative Assay, Western Blot

Journal: Frontiers in Cell and Developmental Biology

Article Title: Lactate promotes mitochondrial biogenesis and fusion via GPR81 to enhance synaptic plasticity-related protein expression in hippocampal cells

doi: 10.3389/fcell.2026.1929409

Figure Lengend Snippet: Effects of SR-18292 and MF18 on the opening of mPTP on in Neuro-2A cells. (a-d) Full-field overview images of monolayer cells. (b-e) Higher magnification cropped images with rectangular boxes indicating the neurite regions of interest (ROIs) used for fluorescence quantification; the soma was excluded from analysis. (c-f) Bar graphs depict the quantification of mPTP, determined by the fluorescence intensity from three replicates. Data are expressed as mean ± SD. Statistical significance: *** p < 0.001 versus the LA group. ### p < 0.001 versus the 3OBA group.

Article Snippet: PGC-1α inhibitor SR-18292 (Selleck, S8528) or mitochondrial fusion inhibitor MF18 (Med Chem Express, HY-150031) was applied 30 min before L-lactate/3OBA.

Techniques: Fluorescence, Analysis

Journal: Frontiers in Cell and Developmental Biology

Article Title: Lactate promotes mitochondrial biogenesis and fusion via GPR81 to enhance synaptic plasticity-related protein expression in hippocampal cells

doi: 10.3389/fcell.2026.1929409

Figure Lengend Snippet: Effects of SR-18292 and MF18 on MMP in Neuro-2A cells. (a) Images show JC-1 staining representative of mitochondrial membrane potential (scale bar = 100 μm), where red and green fluorescence correspond to JC-1 aggregates and monomers, respectively. (b) Bar graphs depict the quantification of mitochondrial membrane potential, determined by the fluorescence intensity ratio (red/green) from three replicates. Data are expressed as mean ± SD. Statistical significance: * p < 0.05, ** p < 0.01 versus the LA group. ## p < 0.01 versus the 3OBA group.

Article Snippet: PGC-1α inhibitor SR-18292 (Selleck, S8528) or mitochondrial fusion inhibitor MF18 (Med Chem Express, HY-150031) was applied 30 min before L-lactate/3OBA.

Techniques: Staining, Membrane, Fluorescence

Journal: Frontiers in Cell and Developmental Biology

Article Title: Lactate promotes mitochondrial biogenesis and fusion via GPR81 to enhance synaptic plasticity-related protein expression in hippocampal cells

doi: 10.3389/fcell.2026.1929409

Figure Lengend Snippet: Effects of SR-18292 and MF18 on OXPHOS transcripts and ATP production in Neuro-2A cells. (a-e) Quantitative analysis (qRT-PCR) of NDUFS8 , SDHb , Uqcrc1 , COX5b , and Atp5a1 transcript levels, derived from three independent replicates. (f) Quantification of relative ATP levels, derived from six independent replicates. Data are expressed as mean ± SD. Statistical significance: * p < 0.05, ** p < 0.01, *** p < 0.001 versus the LA group. # p < 0.05, ## p < 0.01, ### p < 0.001 versus the 3OBA group. n. s., no significant difference.

Article Snippet: PGC-1α inhibitor SR-18292 (Selleck, S8528) or mitochondrial fusion inhibitor MF18 (Med Chem Express, HY-150031) was applied 30 min before L-lactate/3OBA.

Techniques: Analysis, Quantitative RT-PCR, Derivative Assay

Journal: Frontiers in Cell and Developmental Biology

Article Title: Lactate promotes mitochondrial biogenesis and fusion via GPR81 to enhance synaptic plasticity-related protein expression in hippocampal cells

doi: 10.3389/fcell.2026.1929409

Figure Lengend Snippet: Effects of SR-18292 and MF18 on the distribution of mitochondria in neurite of Neuro-2A cells. (a, d) Full-field overview images of monolayer cells. (b, e) Higher magnification cropped images with rectangular boxes indicating the neurite regions of interest (ROIs) used for fluorescence quantification; the soma was excluded from analysis. (c, f) Bar graphs depict the quantification of fluorescence intensity, derived from three independent replicates. Data are expressed as mean ± SD. Statistical significance: *** p < 0.001 versus the LA group. ## p < 0.01, ### p < 0.001 versus the 3OBA group.

Article Snippet: PGC-1α inhibitor SR-18292 (Selleck, S8528) or mitochondrial fusion inhibitor MF18 (Med Chem Express, HY-150031) was applied 30 min before L-lactate/3OBA.

Techniques: Fluorescence, Analysis, Derivative Assay