Metabolomic Phenotypes Reflect Patient Sex and Injury Status: A Cross-Sectional Analysis of Human Synovial Fluid.
biomarkers
cartilage
knee
osteoarthritis
Journal
bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
04 Feb 2023
04 Feb 2023
Historique:
entrez:
27
2
2023
pubmed:
28
2
2023
medline:
28
2
2023
Statut:
epublish
Résumé
Post-traumatic osteoarthritis (PTOA) is caused by knee injuries like anterior cruciate ligament (ACL) injuries. Often, ACL injuries are accompanied by damage to other tissues and structures within the knee including the meniscus. Both are known to cause PTOA but underlying cellular mechanisms driving disease remain unknown. Aside from injury, patient sex is a prevalent risk factor associated with PTOA. Metabolic phenotypes of synovial fluid that differ by knee injury pathology and participant sex will be distinct from each other. A cross-sectional study. Synovial fluid from n=33 knee arthroscopy patients between 18 and 70 years with no prior knee injuries was obtained pre-procedure and injury pathology assigned post-procedure. Synovial fluid was extracted and analyzed via liquid chromatography mass spectrometry metabolomic profiling to examine differences in metabolism between injury pathologies and participant sex. Additionally, samples were pooled and underwent fragmentation to identify metabolites. Metabolite profiles revealed that injury pathology phenotypes were distinct from each other where differences in endogenous repair pathways that are triggered post-injury were detected. Specifically, acute differences in metabolism mapped to amino acid metabolism, lipid-related oxidative metabolism, and inflammatory-associated pathways. Lastly, sexual dimorphic metabolic phenotypes were examined between male and female participants, and within injury pathology. Specifically, Cervonyl Carnitine and other identified metabolites differed in concentration between sexes. The results of this study suggest that different injuries (e.g., ligament vs. meniscus), as well as sex are associated with distinct metabolic phenotypes. Considering these phenotypic associations, a greater understanding of metabolic mechanisms associated with specific injuries and PTOA development may yield data regarding how endogenous repair pathways differ between injury types. Furthermore, ongoing metabolomic analysis of synovial fluid in injured male and female patients can be performed to monitor PTOA development and progression. Extension of this work may potentially lead to the identification of biomarkers as well as drug targets that slow, stop, or reverse PTOA progression based on injury type and patient sex.
Sections du résumé
Background
UNASSIGNED
Post-traumatic osteoarthritis (PTOA) is caused by knee injuries like anterior cruciate ligament (ACL) injuries. Often, ACL injuries are accompanied by damage to other tissues and structures within the knee including the meniscus. Both are known to cause PTOA but underlying cellular mechanisms driving disease remain unknown. Aside from injury, patient sex is a prevalent risk factor associated with PTOA.
Hypothesis
UNASSIGNED
Metabolic phenotypes of synovial fluid that differ by knee injury pathology and participant sex will be distinct from each other.
Study Design
UNASSIGNED
A cross-sectional study.
Methods
UNASSIGNED
Synovial fluid from n=33 knee arthroscopy patients between 18 and 70 years with no prior knee injuries was obtained pre-procedure and injury pathology assigned post-procedure. Synovial fluid was extracted and analyzed via liquid chromatography mass spectrometry metabolomic profiling to examine differences in metabolism between injury pathologies and participant sex. Additionally, samples were pooled and underwent fragmentation to identify metabolites.
Results
UNASSIGNED
Metabolite profiles revealed that injury pathology phenotypes were distinct from each other where differences in endogenous repair pathways that are triggered post-injury were detected. Specifically, acute differences in metabolism mapped to amino acid metabolism, lipid-related oxidative metabolism, and inflammatory-associated pathways. Lastly, sexual dimorphic metabolic phenotypes were examined between male and female participants, and within injury pathology. Specifically, Cervonyl Carnitine and other identified metabolites differed in concentration between sexes.
Conclusions
UNASSIGNED
The results of this study suggest that different injuries (e.g., ligament vs. meniscus), as well as sex are associated with distinct metabolic phenotypes. Considering these phenotypic associations, a greater understanding of metabolic mechanisms associated with specific injuries and PTOA development may yield data regarding how endogenous repair pathways differ between injury types. Furthermore, ongoing metabolomic analysis of synovial fluid in injured male and female patients can be performed to monitor PTOA development and progression.
Clinical Relevance
UNASSIGNED
Extension of this work may potentially lead to the identification of biomarkers as well as drug targets that slow, stop, or reverse PTOA progression based on injury type and patient sex.
Identifiants
pubmed: 36846378
doi: 10.1101/2023.02.03.527040
pmc: PMC9959930
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM103474
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR073964
Pays : United States
Organisme : NIH HHS
ID : S10 OD028650
Pays : United States
Commentaires et corrections
Type : UpdateIn
Déclaration de conflit d'intérêts
Conflicts of Interest Authors have no conflicts of interest to disclose.
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