The impact of aging on achilles tendon ossification in mice.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40437419", "kind": "science-record", "revision": 4, "content_hash": "sha256:5bd9902fc70048bede447086d077250442e8e0e1720810d8cbf8f89afcf04cbe", "created_at": "2026-11-01T20:30:34Z", "updated_at": "2026-11-01T22:56:35Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The impact of aging on achilles tendon ossification in mice.", "doi": "10.1186/s12891-025-08788-5", "pmid": "40437419", "authors": ["Hanhua Cai", "Yujian Lan", "Huan Liu", "Qi Hao"], "journal": "BMC musculoskeletal disorders", "year": 2025, "abstract": "BACKGROUND: Heterotopic ossification is a frequent complication of soft tissue injuries, particularly in tendons. Although ossification in tendon tissue has been reported in a range of aging and disease models, the underlying biomarkers and mechanisms remain unknown. And the characterisation and sensitivity of previous diagnostic biomarkers for tendon ectopic ossification do not meet the demands of clinical use. The aim of this study was to characterise the effects of aging on ossification in the mouse Achilles tendon and to identify characteristic genes and therapeutic targets for tendon ossification in mice by using a machine learning approach.\nMETHODS: We retrieved the transcriptome profile of GSE126118 from the Gene Expression Omnibus (GEO) database. Following background correction and normalization using the transcripts per million (TPM) method, differentially expressed genes (DEGs) were identified with the limma R package (p < 0.05, |log2FC| > 1). Subsequently, 468 senescence genes were downloaded from the Aging Atlas database, and senescence-associated DEGs (HO senescence genes) were identified. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) network analyses were conducted on the identified DEGs. To further refine the HO aging signature, support vector machine (SVM) regression was employed. Additionally, we predicted transcription factors, miRNAs, and small molecule drugs potentially associated with the characterized genes.\nRESULTS: Three characterised genes were identified as biomarkers associated with ectopic ossification and aging in the mouse Achilles tendon, Atp5o, Mmp2 and Mmp13. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed significant enrichment in processes related to cartilage endochondral ossification, metalloendopeptidase activity, and mitochondrial proton transport ATP synthase complex. Additionally, HIF-1 and GnRH signaling pathways were prominently represented among the differentially expressed genes.\nCONCLUSION: Atp5o, Mmp2 and Mmp13 were identified as relevant signature genes for the effects of aging on Achilles tendon ossification in mice. Atp5o, Mmp2, and Mmp13 may influence tendon ossification by affecting mitochondrial function as well as extracellular matrix degradation to regulate senescence. This finding suggests a potential link between these processes, opening new avenues for research into diagnostic markers and therapeutic targets. These genes hold promise for the development of novel treatments for tendon ossification, a debilitating condition currently lacking effective therapeutic options.", "claims": [{"id": "claim-method", "statement": "Subsequently, differentially expressed genes (DEGs) were identified with the limma R package. The Benjamini and Hochberg (BH) procedure was employed to control the false discovery rate (FDR) while identifying significant DEGs, with thresholds set at p < 0.05 and |log2 fold change (FC)| > 1.0.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40437419", "locator": "sections[4] \"Data preprocessing and differential expression analysis\" paragraph 2", "quote": "Subsequently, differentially expressed genes (DEGs) were identified with the limma R package. The Benjamini and Hochberg (BH) procedure was employed to control the false discovery rate (FDR) while identifying significant DEGs, with thresholds set at p < 0.05 and |log2 fold change (FC)| > 1.0."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analysed during the current study can be found in the GEO repository [https://www.ncbi.nlm.nih.gov/geo/].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40437419", "locator": "sections[23] \"Data availability\" paragraph 2", "quote": "The datasets analysed during the current study can be found in the GEO repository [https://www.ncbi.nlm.nih.gov/geo/]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Three characterised genes were identified as biomarkers associated with ectopic ossification and aging in the mouse Achilles tendon, Atp5o, Mmp2 and Mmp13.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40437419", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Three characterised genes were identified as biomarkers associated with ectopic ossification and aging in the mouse Achilles tendon, Atp5o, Mmp2 and Mmp13."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Three characterised genes were identified as biomarkers associated with ectopic ossification and aging in the mouse Achilles tendon, Atp5o, Mmp2 and Mmp13.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40437419"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE126118"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE126118"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40437419", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12891-025-08788-5", "sha256": "sha256:abc0e9070d19bd6dcfaae448229c27d102dd2f4d2d3d0f1be4ccb51dc2270711", "bytes": 34865, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12891-025-08788-5", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12117786", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE126118", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE126118", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE126118", "version": null, "note": "The datasets analysed during the current study can be found in the GEO repository [https://www.ncbi.nlm.nih.gov/geo/].", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analysed during the current study can be found in the GEO repository [https://www.ncbi.nlm.nih.gov/geo/].", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3591835", "GSM3591836", "GSM3591837", "GSM3591838", "GSM3591839", "GSM3591840", "GSM3591841"], "sample_count": 7, "group_sizes": null, "group_sizes_basis": null, "platform": "13112", "taxon": "Mus musculus", "title": "Coordinating Tissue Regeneration through TGF-β Activated Kinase 1 (TAK1) In-activation and Re-activation", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE126118 not downloaded", "asset:data:geo:GSE126118 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Subsequently, differentially expressed genes (DEGs) were identified with the limma R package. The Benjamini and Hochberg (BH) procedure was employed to control the false discovery rate (FDR) while identifying significant DEGs, with thresholds set at p < 0.05 and |log2 fold change (FC)| > 1.0."}}, {"id": "method-2", "family": "machine_learning", "specific": "support_vector_machine", "label": "Machine learning", "dsl_operations": ["train_classifier", "cross_validate", "roc_auc"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 0.7, "band": "medium", "quote": "support vector machine"}}, {"id": "method-3", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}, {"id": "method-4", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "pathway enrichment"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:40437419", "data:geo:GSE126118"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE126118"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:53:27Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9542, "completion_tokens": 1652, "cached_tokens": 128}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:40437419", "type": "paper", "label": "pmid:40437419"}, {"id": "source:pmid:40437419", "type": "manuscript", "label": "PMID 40437419 full text"}, {"id": "data:geo:GSE126118", "type": "dataset", "label": "GEO GSE126118"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40437419", "type": "paper", "label": "pmid:40437419"}, {"id": "source:pmid:40437419", "type": "manuscript", "label": "PMID 40437419 full text"}, {"id": "data:geo:GSE126118", "type": "dataset", "label": "GEO GSE126118"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40437419", "type": "extraction", "used": ["source:pmid:40437419"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE126118", "type": "accession_resolution", "used": ["data:geo:GSE126118"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:40437419", "parent_hash": "sha256:36df2d96b37ade2bc9b365ae18d4e584dbb6d0d30d4511ee8ad18eb1e75efccc", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE126118 licence not read", "asset:data:geo:GSE126118 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["act of aging on achilles tendon ossification in mice.", "cterise the effects of aging on ossification in the mouse Achilles tendon and to identify characterist", "therapeutic targets for tendon ossification in mice by using a machine learning approach. 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