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pmid:33283469

Serum MicroRNA Differences Between Fracture in Postmenopausal Women with and without Diabetes.

Cheng Ren · Ming Li · Liang Sun · Zhong Li · Yao Lu · Qian Wang · Teng Ma · Han-Zhong Xue · Kun Zhang

Orthopaedic surgery · 2021 doi:10.1111/os.12866

Paper

complete

Experiment

partial

Data

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Analysis

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:33283469
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science-record
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2026-11-01T15:41:18Z
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2026-11-01T22:45:44Z
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title
Serum MicroRNA Differences Between Fracture in Postmenopausal Women with and without Diabetes.
doi
10.1111/os.12866
pmid
33283469
authors array · 9 items
[0]
Cheng Ren
[1]
Ming Li
[2]
Liang Sun
[3]
Zhong Li
[4]
Yao Lu
[5]
Qian Wang
[6]
Teng Ma
[7]
Han-Zhong Xue
[8]
Kun Zhang
journal
Orthopaedic surgery
year
2021
abstract
OBJECTIVE: To screen serum microRNAs (miRNAs) which could discriminate fracture status in postmenopausal women with or without diabetes. METHODS: The miRNA expression profile dataset GSE70318 was downloaded from Gene Expression Omnibus (GEO) database. This dataset composed of 74 samples, among these, 55 postmenopausal women was selected for bioinformatics analysis, including 19 osteoporotic fracture patients with type-2 diabetes, 19 osteoporotic fracture patients without type-2 diabetes, and 17 healthy control subjects. These samples were divided into two groups: fracture patients with diabetes vs healthy subjects (FH group) and fracture patients without diabetes vs healthy subjects (DFH group). Then, the differentially expressed miRNA (DEMs) in FH group and DFH group were respectively identified. The target genes of DEMs were predicted, followed by functional enrichment analysis. Furthermore, DEMs related to long non-coding RNAs (lncRNAs) were screened, and DEMs-lncRNA-target genes network was constructed. Subsequently, principal component analysis (PCA) of DEMs was performed to further explore the expression characteristics of the selected miRNAs in different types of fracture samples. Finally, the expression level of significant DEMs was calculated by quantitative real-time polymerase chain reaction (qPCR) to verify the accuracy of the results of bioinformatics analysis. RESULTS: A total of 18 and 23 DEMs were identified in FH and DFH groups, respectively. Gene ontology (GO) analysis showed that genes in FH group were significantly enriched in regulation of transcription (GO: 0045449) and genes in DFH group were mainly enriched in cellular response to hormone stimulus (GO: 0032870). Meanwhile, pathway analysis indicated that genes in FH group were primarily enriched in T cell receptor signaling pathway (hsa04660) and genes in DFH group were mainly implicated in neurotrophin-signaling pathway (hsa04722). Moreover, the miRNA-lncRNA analysis revealed that miR-155-5p regulated by lncRNA MIR155HG was up-regulated in FH group; in addition, the miR-181c was significantly up-regulated and miR-375 was observably down-regulated in DFH group. Furthermore, PCA analysis suggested that the screened miRNAs were able to differentiate these two types of fractures in postmenopausal women. The miR-181c and miR-375 might be regarded as potential predictors for fracture, while miR-155-5p might be a candidate diagnostic biomarker for diabetic fracture. Finally, the results of qPCR were consistent with that of microarray data. CONCLUSIONS: Overall, these three miRNAs might be regarded as potential diagnostic biomarkers to discriminate fracture status in postmenopausal women with and or without diabetes, and they served a putative role in the pathogenesis of these two diseases. However, these findings were only observed in serum samples and further clinical trials are urgently demanded to validate our results.
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The DEMs in FH and DFH groups were identified using limma package, respectively.
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sections[5] "Data Preprocessing and Differential Expression Analysis" paragraph 2
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The DEMs in FH and DFH groups were identified using limma package, respectively.
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The results of GO function analysis for DEMs in three groups (Top 5 listed)
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[3]
2.64E‐02
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itative real-time polymerase chain reaction (qPCR) to verify the accuracy of the results of bi
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r diabetic fracture. Finally, the results of qPCR were consistent with that of microarray data
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results of qPCR were consistent with that of microarray data. CONCLUSIONS: Overall, these three miRN
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33283469", "kind": "science-record", "revision": 8, "content_hash": "sha256:dbbaab1903249e2a83546ace5cf9ceedccbdfcdf4be8a5e9039309c07c6d01cd", "created_at": "2026-11-01T15:41:18Z", "updated_at": "2026-11-01T22:45:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Serum MicroRNA Differences Between Fracture in Postmenopausal Women with and without Diabetes.", "doi": "10.1111/os.12866", "pmid": "33283469", "authors": ["Cheng Ren", "Ming Li", "Liang Sun", "Zhong Li", "Yao Lu", "Qian Wang", "Teng Ma", "Han-Zhong Xue", "Kun Zhang"], "journal": "Orthopaedic surgery", "year": 2021, "abstract": "OBJECTIVE: To screen serum microRNAs (miRNAs) which could discriminate fracture status in postmenopausal women with or without diabetes.\nMETHODS: The miRNA expression profile dataset GSE70318 was downloaded from Gene Expression Omnibus (GEO) database. This dataset composed of 74 samples, among these, 55 postmenopausal women was selected for bioinformatics analysis, including 19 osteoporotic fracture patients with type-2 diabetes, 19 osteoporotic fracture patients without type-2 diabetes, and 17 healthy control subjects. These samples were divided into two groups: fracture patients with diabetes vs healthy subjects (FH group) and fracture patients without diabetes vs healthy subjects (DFH group). Then, the differentially expressed miRNA (DEMs) in FH group and DFH group were respectively identified. The target genes of DEMs were predicted, followed by functional enrichment analysis. Furthermore, DEMs related to long non-coding RNAs (lncRNAs) were screened, and DEMs-lncRNA-target genes network was constructed. Subsequently, principal component analysis (PCA) of DEMs was performed to further explore the expression characteristics of the selected miRNAs in different types of fracture samples. Finally, the expression level of significant DEMs was calculated by quantitative real-time polymerase chain reaction (qPCR) to verify the accuracy of the results of bioinformatics analysis.\nRESULTS: A total of 18 and 23 DEMs were identified in FH and DFH groups, respectively. Gene ontology (GO) analysis showed that genes in FH group were significantly enriched in regulation of transcription (GO: 0045449) and genes in DFH group were mainly enriched in cellular response to hormone stimulus (GO: 0032870). Meanwhile, pathway analysis indicated that genes in FH group were primarily enriched in T cell receptor signaling pathway (hsa04660) and genes in DFH group were mainly implicated in neurotrophin-signaling pathway (hsa04722). Moreover, the miRNA-lncRNA analysis revealed that miR-155-5p regulated by lncRNA MIR155HG was up-regulated in FH group; in addition, the miR-181c was significantly up-regulated and miR-375 was observably down-regulated in DFH group. Furthermore, PCA analysis suggested that the screened miRNAs were able to differentiate these two types of fractures in postmenopausal women. The miR-181c and miR-375 might be regarded as potential predictors for fracture, while miR-155-5p might be a candidate diagnostic biomarker for diabetic fracture. Finally, the results of qPCR were consistent with that of microarray data.\nCONCLUSIONS: Overall, these three miRNAs might be regarded as potential diagnostic biomarkers to discriminate fracture status in postmenopausal women with and or without diabetes, and they served a putative role in the pathogenesis of these two diseases. However, these findings were only observed in serum samples and further clinical trials are urgently demanded to validate our results.", "claims": [{"id": "claim-method", "statement": "The DEMs in FH and DFH groups were identified using limma package, respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33283469", "locator": "sections[5] \"Data Preprocessing and Differential Expression Analysis\" paragraph 2", "quote": "The DEMs in FH and DFH groups were identified using limma package, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "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:33283469"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33283469", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1111/os.12866", "sha256": 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pathway", "ITK, CARD11, FOS, KRAS, GSK3B…", "8", "2.45E‐04"], ["hsa04662:B cell receptor signaling pathway", "CARD11, FOS, KRAS, GSK3B, PIK3C…", "7", "2.24E‐04"], ["hsa04910:Insulin signaling pathway", "KRAS, GSK3B, SOCS1, PRKAR1A, RHEB…", "9", "1.60E‐04"], ["hsa04722:Neurotrophin signaling pathway", "YWHAZ, KRAS, GSK3B, PIK3CA, RAP1B…", "7", "3.18E‐03"], ["hsa04150:mTOR signaling pathway", "YWHAZ, KRAS, GSK3B, PIK3CA, RAP1B…", "5", "3.11E‐03"], ["DFH", "hsa04722:Neurotrophin signaling pathway", "IRS2, YWHAZ, YWHAH, CAMK2D, IRS1…", "6", "3.65E‐03"], ["hsa04920:Adipocytokine signaling pathway", "IRS2, JAK2, ACSL3, IRS1", "4", "1.85E‐02"], ["hsa04540:Gap junction", "EGFR, ADCY9, PDGFC, GNAS", "4", "3.87E‐02"], ["hsa04960:Aldosterone‐regulated sodium reabsorption", "EGFR, ADCY9, PDGFC, GNAS", "3", "4.65E‐02"], ["hsa04912:GnRH signaling pathway", "EGFR, ADCY9, CAMK2D, GNAS", "4", "4.92E‐02"], ["co‐DEMs", "hsa04612:Antigen processing and presentation", "HSP90AA1, HSPA5", "2", "1.93E‐03"], ["hsa04914:Progesterone‐mediated oocyte maturation", "CDK1, HSP90AA1", "2", "1.99E‐02"], ["hsa04666:Fc gamma R‐mediated phagocytosis", "MYO10, MARCKS", "2", "2.18E‐02"]], "row_count": 14, "column_count": 5, "numeric_cells": 44, "header_rows": 1, "locator": "section[16]/table-wrap[2]#os12866-tbl-0002"}}], "gaps": []}, "analysis": {"state": "partial", "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": "The DEMs in FH and DFH groups were identified using limma package, respectively."}}, {"id": "method-2", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": [], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:33283469", "asset:table:pmid:33283469:1", "asset:table:pmid:33283469:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T19:17:54Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 32301, "completion_tokens": 1587, "cached_tokens": 792}}, "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:33283469", "type": "paper", "label": "pmid:33283469"}, {"id": "source:pmid:33283469", "type": "manuscript", "label": "PMID 33283469 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33283469", "type": "paper", "label": "pmid:33283469"}, {"id": "source:pmid:33283469", "type": "manuscript", "label": "PMID 33283469 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33283469", "type": "extraction", "used": ["source:pmid:33283469"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "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:33283469", "parent_hash": "sha256:725b787f16bc6afdb78ff276305554bde5513c25061f57dd93f3c3f662f5f540", "fork_of": null, "generation": 7}, "gaps": ["execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["itative real-time polymerase chain reaction (qPCR) to verify the accuracy of the results of bi", "r diabetic fracture. Finally, the results of qPCR were consistent with that of microarray data", "plied to compare the differences between the qPCR results of two groups. P < 0.05 was consider", "clinical characteristics of patients used in qPCR verification Table S2. The primer sequences"], "order_basis": "paper_text_order:1375", "id": "assay:1"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["results of qPCR were consistent with that of microarray data. CONCLUSIONS: Overall, these three miRN"], "order_basis": "paper_text_order:2586", "id": "assay:2"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The DEMs in FH and DFH groups were identified using limma package, respectively."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}