Serum Metabolomic Signatures for Knee Cartilage Volume Loss over 10 Years in Community-Dwelling Older Adults
Osteoarthritis (OA) is the most prevalent joint disorder characterized by joint structural pathological changes with the loss of articular cartilage as its hallmark. Tools that can predict cartilage loss would help identify people at high risk, thus preventing OA development. The recent advance of t...
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MDPI AG
2022-06-01
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| author | Zikun Xie Dawn Aitken Ming Liu Guanghua Lei Graeme Jones Flavia Cicuttini Guangju Zhai |
| author_facet | Zikun Xie Dawn Aitken Ming Liu Guanghua Lei Graeme Jones Flavia Cicuttini Guangju Zhai |
| author_sort | Zikun Xie |
| collection | DOAJ |
| description | Osteoarthritis (OA) is the most prevalent joint disorder characterized by joint structural pathological changes with the loss of articular cartilage as its hallmark. Tools that can predict cartilage loss would help identify people at high risk, thus preventing OA development. The recent advance of the metabolomics provides a new avenue to systematically investigate metabolic alterations in disease and identify biomarkers for early diagnosis. Using a metabolomics approach, the current study aimed to identify serum metabolomic signatures for predicting knee cartilage volume loss over 10 years in the Tasmania Older Adult Cohort (TASOAC). Cartilage volume was measured in the medial, lateral, and patellar compartments of the knee by MRI at baseline and follow-up. Changes in cartilage volume over 10 years were calculated as percentage change per year. Fasting serum samples collected at 2.6-year follow-up were metabolomically profiled using the TMIC Prime Metabolomics Profiling Assay and pairwise metabolite ratios as the proxies of enzymatic reaction were calculated. Linear regression was used to identify metabolite ratio(s) associated with change in cartilage volume in each of the knee compartments with adjustment for age, sex, and BMI. The significance level was defined at α = 3.0 × 10<sup>−6</sup> to control multiple testing. A total of 344 participants (51% females) were included in the study. The mean age was 62.83 ± 6.13 years and the mean BMI was 27.48 ± 4.41 kg/m<sup>2</sup> at baseline. The average follow-up time was 10.84 ± 0.66 years. Cartilage volume was reduced by 1.34 ± 0.72%, 1.06 ± 0.58%, and 0.98 ± 0.46% per year in the medial, lateral, and patellar compartments, respectively. Our data showed that the increased ratios of hexadecenoylcarnitine (C16:1) to tetradecanoylcarnitine (C14) and C16:1 to dodecanoylcarnitine (C12) were associated with 0.12 ± 0.02% reduction per year in patellar cartilage volume (both <i>p</i> < 3.03 × 10<sup>−6</sup>). In conclusion, our data suggested that alteration of long chain fatty acid β-oxidation was involved in patellar cartilage loss. While confirmation is needed, the ratios of C16:1 to C14 and C12 might be used to predict long-term cartilage loss. |
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| spelling | doaj.art-ef180c4c1077450c9bf996780b48e27f2023-11-23T17:36:51ZengMDPI AGLife2075-17292022-06-0112686910.3390/life12060869Serum Metabolomic Signatures for Knee Cartilage Volume Loss over 10 Years in Community-Dwelling Older AdultsZikun Xie0Dawn Aitken1Ming Liu2Guanghua Lei3Graeme Jones4Flavia Cicuttini5Guangju Zhai6Division of Biomedical Sciences (Genetics), Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaMenzies Institute for Medical Research, University of Tasmania, Hobart 7005, AustraliaDivision of Biomedical Sciences (Genetics), Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaXiangya Hospital, Central South University, Changsha 410008, ChinaMenzies Institute for Medical Research, University of Tasmania, Hobart 7005, AustraliaDepartment of Epidemiology and Preventive Medicine, Monash University Medical School, Melbourne 3006, AustraliaDivision of Biomedical Sciences (Genetics), Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, CanadaOsteoarthritis (OA) is the most prevalent joint disorder characterized by joint structural pathological changes with the loss of articular cartilage as its hallmark. Tools that can predict cartilage loss would help identify people at high risk, thus preventing OA development. The recent advance of the metabolomics provides a new avenue to systematically investigate metabolic alterations in disease and identify biomarkers for early diagnosis. Using a metabolomics approach, the current study aimed to identify serum metabolomic signatures for predicting knee cartilage volume loss over 10 years in the Tasmania Older Adult Cohort (TASOAC). Cartilage volume was measured in the medial, lateral, and patellar compartments of the knee by MRI at baseline and follow-up. Changes in cartilage volume over 10 years were calculated as percentage change per year. Fasting serum samples collected at 2.6-year follow-up were metabolomically profiled using the TMIC Prime Metabolomics Profiling Assay and pairwise metabolite ratios as the proxies of enzymatic reaction were calculated. Linear regression was used to identify metabolite ratio(s) associated with change in cartilage volume in each of the knee compartments with adjustment for age, sex, and BMI. The significance level was defined at α = 3.0 × 10<sup>−6</sup> to control multiple testing. A total of 344 participants (51% females) were included in the study. The mean age was 62.83 ± 6.13 years and the mean BMI was 27.48 ± 4.41 kg/m<sup>2</sup> at baseline. The average follow-up time was 10.84 ± 0.66 years. Cartilage volume was reduced by 1.34 ± 0.72%, 1.06 ± 0.58%, and 0.98 ± 0.46% per year in the medial, lateral, and patellar compartments, respectively. Our data showed that the increased ratios of hexadecenoylcarnitine (C16:1) to tetradecanoylcarnitine (C14) and C16:1 to dodecanoylcarnitine (C12) were associated with 0.12 ± 0.02% reduction per year in patellar cartilage volume (both <i>p</i> < 3.03 × 10<sup>−6</sup>). In conclusion, our data suggested that alteration of long chain fatty acid β-oxidation was involved in patellar cartilage loss. While confirmation is needed, the ratios of C16:1 to C14 and C12 might be used to predict long-term cartilage loss.https://www.mdpi.com/2075-1729/12/6/869knee osteoarthritisMRImetabolomicsacylcarnitines |
| spellingShingle | Zikun Xie Dawn Aitken Ming Liu Guanghua Lei Graeme Jones Flavia Cicuttini Guangju Zhai Serum Metabolomic Signatures for Knee Cartilage Volume Loss over 10 Years in Community-Dwelling Older Adults Life knee osteoarthritis MRI metabolomics acylcarnitines |
| title | Serum Metabolomic Signatures for Knee Cartilage Volume Loss over 10 Years in Community-Dwelling Older Adults |
| title_full | Serum Metabolomic Signatures for Knee Cartilage Volume Loss over 10 Years in Community-Dwelling Older Adults |
| title_fullStr | Serum Metabolomic Signatures for Knee Cartilage Volume Loss over 10 Years in Community-Dwelling Older Adults |
| title_full_unstemmed | Serum Metabolomic Signatures for Knee Cartilage Volume Loss over 10 Years in Community-Dwelling Older Adults |
| title_short | Serum Metabolomic Signatures for Knee Cartilage Volume Loss over 10 Years in Community-Dwelling Older Adults |
| title_sort | serum metabolomic signatures for knee cartilage volume loss over 10 years in community dwelling older adults |
| topic | knee osteoarthritis MRI metabolomics acylcarnitines |
| url | https://www.mdpi.com/2075-1729/12/6/869 |
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