The impact of aging on achilles tendon ossification in mice
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...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-05-01
|
| Series: | BMC Musculoskeletal Disorders |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12891-025-08788-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849704135969996800 |
|---|---|
| author | Hanhua Cai Yujian Lan Huan Liu Qi Hao |
| author_facet | Hanhua Cai Yujian Lan Huan Liu Qi Hao |
| author_sort | Hanhua Cai |
| collection | DOAJ |
| description | 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. Methods 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. Results 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. Conclusion 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. |
| format | Article |
| id | doaj-art-b01bf6d52e114dc79330c99f518aac8c |
| institution | DOAJ |
| issn | 1471-2474 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Musculoskeletal Disorders |
| spelling | doaj-art-b01bf6d52e114dc79330c99f518aac8c2025-08-20T03:16:52ZengBMCBMC Musculoskeletal Disorders1471-24742025-05-0126111210.1186/s12891-025-08788-5The impact of aging on achilles tendon ossification in miceHanhua Cai0Yujian Lan1Huan Liu2Qi Hao3Department of Orthopedics, Affiliated Hospital of Putian UniversityDepartment of Orthopaedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityDepartment of Orthopaedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityDepartment of Orthopaedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical UniversityAbstract 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. Methods 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. Results 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. Conclusion 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.https://doi.org/10.1186/s12891-025-08788-5AgingAchilles tendon ossificationBiomarkersGOKEGGPPI |
| spellingShingle | Hanhua Cai Yujian Lan Huan Liu Qi Hao The impact of aging on achilles tendon ossification in mice BMC Musculoskeletal Disorders Aging Achilles tendon ossification Biomarkers GO KEGG PPI |
| title | The impact of aging on achilles tendon ossification in mice |
| title_full | The impact of aging on achilles tendon ossification in mice |
| title_fullStr | The impact of aging on achilles tendon ossification in mice |
| title_full_unstemmed | The impact of aging on achilles tendon ossification in mice |
| title_short | The impact of aging on achilles tendon ossification in mice |
| title_sort | impact of aging on achilles tendon ossification in mice |
| topic | Aging Achilles tendon ossification Biomarkers GO KEGG PPI |
| url | https://doi.org/10.1186/s12891-025-08788-5 |
| work_keys_str_mv | AT hanhuacai theimpactofagingonachillestendonossificationinmice AT yujianlan theimpactofagingonachillestendonossificationinmice AT huanliu theimpactofagingonachillestendonossificationinmice AT qihao theimpactofagingonachillestendonossificationinmice AT hanhuacai impactofagingonachillestendonossificationinmice AT yujianlan impactofagingonachillestendonossificationinmice AT huanliu impactofagingonachillestendonossificationinmice AT qihao impactofagingonachillestendonossificationinmice |