Dataset Information

Serum Metabolite Profiles Are Altered by Erlotinib Treatment and the Integrin ?1-Null Genotype but Not by Post-Traumatic Osteoarthritis.

ABSTRACT: The risk of developing post-traumatic osteoarthritis (PTOA) following joint injury is high. Furthering our understanding of the molecular mechanisms underlying PTOA and/or identifying novel biomarkers for early detection may help to improve treatment outcomes. Increased expression of integrin ?1?1 and inhibition of epidermal growth factor receptor (EGFR) signaling protect the knee from spontaneous OA; however, the impact of the integrin ?1?1/EGFR axis on PTOA is currently unknown. We sought to determine metabolic changes in serum samples collected from wild-type and integrin ?1-null mice that underwent surgery to destabilize the medial meniscus and were treated with the EGFR inhibitor erlotinib. Following (1)H nuclear magnetic resonance spectroscopy, we generated multivariate statistical models that distinguished between the metabolic profiles of erlotinib- versus vehicle-treated mice and the integrin ?1-null versus wild-type mouse genotype. Our results show the sex-dependent effects of erlotinib treatment and highlight glutamine as a metabolite that counteracts this treatment. Furthermore, we identified a set of metabolites associated with increased reactive oxygen species production, susceptibility to OA, and regulation of TRP channels in ?1-null mice. Our study indicates that systemic pharmacological and genetic factors have a greater effect on serum metabolic profiles than site-specific factors such as surgery.

SUBMITTER: Mickiewicz B

PROVIDER: S-EPMC4779398 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Serum Metabolite Profiles Are Altered by Erlotinib Treatment and the Integrin α1-Null Genotype but Not by Post-Traumatic Osteoarthritis.

Mickiewicz Beata B Shin Sung Y SY Pozzi Ambra A Vogel Hans J HJ Clark Andrea L AL

Journal of proteome research 20160128 3

The risk of developing post-traumatic osteoarthritis (PTOA) following joint injury is high. Furthering our understanding of the molecular mechanisms underlying PTOA and/or identifying novel biomarkers for early detection may help to improve treatment outcomes. Increased expression of integrin α1β1 and inhibition of epidermal growth factor receptor (EGFR) signaling protect the knee from spontaneous OA; however, the impact of the integrin α1β1/EGFR axis on PTOA is currently unknown. We sought to d ...[more]

PMID: 26784366

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Dataset Information

Serum Metabolite Profiles Are Altered by Erlotinib Treatment and the Integrin ?1-Null Genotype but Not by Post-Traumatic Osteoarthritis.

Publications

Serum Metabolite Profiles Are Altered by Erlotinib Treatment and the Integrin α1-Null Genotype but Not by Post-Traumatic Osteoarthritis.

Similar Datasets

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