Serum fatty acid chain length associates with prevalent symptomatic end-stage osteoarthritis, independent of BMI

Meessen, Jennifer; Hosnijeh, Fatemeh Saberi; Hollander, Wouter den; Bom, Johanna G. van der; Hilten, J. A. van; Spil, W.E. van; So‐Osman, Cynthia; Uitterlinden, André G.; Kloppenburg, Margreet; Nelissen, Rob G H H; Duijn, C.M. van; Slagboom, P. Eline; Meurs, Joyce B. J. van; Meulenbelt, Ingrid

doi:10.1038/s41598-020-71811-3

Cited by 10 publications

(12 citation statements)

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“…We also saw an association with D-arginine and D-ornithine metabolism, both enhancers of wound healing in mice [67,68]; intriguingly, there is some evidence that plasma arginine levels are reduced in knee OA patients [69]. Additional associations of interest include fatty acid elongation; serum fatty acid chain length is associated with symptomatic end-stage OA [70], and the bacterial secretion system, which enables the export of bacterial proteases to the extracellular environment in the context of chronic wound establishment [71].…”

Section: Plos Onementioning

confidence: 74%

Ear wound healing in MRL/MpJ mice is associated with gut microbiome composition and is transferable to non-healer mice via microbiome transplantation

et al. 2021

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Objective Adult elastic cartilage has limited repair capacity. MRL/MpJ (MRL) mice, by contrast, are capable of spontaneously healing ear punctures. This study was undertaken to characterize microbiome differences between healer and non-healer mice and to evaluate whether this healing phenotype can be transferred via gut microbiome transplantation. Methods We orally transplanted C57BL/6J (B6) mice with MRL/MpJ cecal contents at weaning and as adults (n = 57) and measured ear hole closure 4 weeks after a 2.0mm punch and compared to vehicle-transplanted MRL and B6 (n = 25) and B6-transplanted MRL (n = 20) mice. Sex effects, timing of transplant relative to earpunch, and transgenerational heritability were evaluated. In a subset (n = 58), cecal microbiomes were profiled by 16S sequencing and compared to ear hole closure. Microbial metagenomes were imputed using PICRUSt. Results Transplantation of B6 mice with MRL microbiota, either in weanlings or adults, improved ear hole closure. B6-vehicle mice healed ear hole punches poorly (0.25±0.03mm, mm ear hole healing 4 weeks after a 2mm ear hole punch [2.0mm—final ear hole size], mean±SEM), whereas MRL-vehicle mice healed well (1.4±0.1mm). MRL-transplanted B6 mice healed roughly three times as well as B6-vehicle mice, and half as well as MRL-vehicle mice (0.74±0.05mm, P = 6.9E-10 vs. B6-vehicle, P = 5.2E-12 vs. MRL-vehicle). Transplantation of MRL mice with B6 cecal material did not reduce MRL healing (B6-transplanted MRL 1.3±0.1 vs. MRL-vehicle 1.4±0.1, p = 0.36). Transplantation prior to ear punch was associated with the greatest ear hole closure. Offspring of transplanted mice healed significantly better than non-transplanted control mice (offspring:0.63±0.03mm, mean±SEM vs. B6-vehicle control:0.25±0.03mm, n = 39 offspring, P = 4.6E-11). Several microbiome clades were correlated with healing, including Firmicutes (R = 0.84, P = 8.0E-7), Lactobacillales (R = 0.65, P = 1.1E-3), and Verrucomicrobia (R = -0.80, P = 9.2E-6). Females of all groups tended to heal better than males (B6-vehicle P = 0.059, MRL-transplanted B6 P = 0.096, offspring of MRL-transplanted B6 P = 0.0038, B6-transplanted MRL P = 1.6E-6, MRL-vehicle P = 0.0031). Many clades characteristic of female mouse cecal microbiota vs. males were the same as clades characteristic of MRL and MRL-transplanted B6 mice vs. B6 controls, including including increases in Clostridia and reductions in Verrucomicrobia in female mice. Conclusion In this study, we found an association between the microbiome and tissue regeneration in MRL mice and demonstrate that this trait can be transferred to non-healer mice via microbiome transplantation. We identified several microbiome clades associated with healing.

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Section: Plos Onementioning

confidence: 74%

Ear wound healing in MRL/MpJ mice is associated with gut microbiome composition and is transferable to non-healer mice via microbiome transplantation

et al. 2021

View full text Add to dashboard Cite

show abstract

“…We also saw an association with D-arginine and D-ornithine metabolism, both enhancers of wound healing in mice [63,64]; intriguingly, there is some evidence that plasma arginine levels are reduced in knee OA patients [65]. Additional associations of interest include fatty acid elongation; serum fatty acid chain length is associated with symptomatic end-stage OA [66], and the bacterial secretion system, which enables the export of bacterial proteases to the extracellular environment in the context of chronic wound establishment [67].…”

Section: Discussionmentioning

confidence: 99%

Ear wound healing in MRL/MpJ mice is associated with gut microbiome composition and is transferable to non-healer mice via microbiome transplantation

Velasco

Dunn

Sturdy

et al. 2021

Preprint

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Objective : Adult cartilage has limited repair capacity. MRL/MpJ mice, by contrast, are capable of spontaneously healing ear punctures. This study was undertaken to characterize microbiome differences between healer and nonhealer mice and to evaluate microbiome transplantation as a novel regenerative therapy. Methods : We transplanted C57BL/6J mice with MRL/MpJ cecal contents in mice at weaning and as adults (n=57) and measured earhole closure 4 weeks after a 2.0mm punch and compared to vehicle-transplanted MRL and B6 (n=25) and B6-transplanted MRL (n=20) mice. Sex effects, timing of transplant relative to earpunch, and transgenerational heritability were evaluated. In a subset (n=58), cecal microbiomes were profiled by 16S sequencing and compared to earhole closure rates. Microbial metagenomes were imputed using PICRUSt. Results : Transplantation of B6 mice with MRL microbiota, either in weanlings or adults, improved earhole closure rates. Transplantation prior to ear punch was associated with the greatest earhole closure. Offspring of transplanted mice healed better than controls. Several microbiome clades were correlated with healing, including Firmicutes, Lactobacillales, and Verrucomicrobia. Gram-negative organisms were reduced. Females of all groups tended to heal better than males, female microbiota resembled MRL mice. Conclusion : In this study, we found an association between the microbiome and tissue regeneration in MRL mice and demonstrate that this trait can be transferred to nonhealer mice via microbiome transplantation. We identified several microbiome clades associated with healing. Future studies should evaluate the mechanisms underlying these findings and confirm our results in murine OA.

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“… Meessen, J. et al. [ 29 ] OA vs. controls Serum UPLC-TQ-MS OA 32 and controls 35 in discovery cohort; OA 30 and controls 30 in replication cohort. Chen R. et al.…”

Section: Methodsmentioning

confidence: 99%

The role of metabolomics in precision medicine of osteoarthritis: How far are we?

Zhai

2021

Osteoarthritis and Cartilage Open

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Serum fatty acid chain length associates with prevalent symptomatic end-stage osteoarthritis, independent of BMI

Cited by 10 publications

References 50 publications

Ear wound healing in MRL/MpJ mice is associated with gut microbiome composition and is transferable to non-healer mice via microbiome transplantation

Ear wound healing in MRL/MpJ mice is associated with gut microbiome composition and is transferable to non-healer mice via microbiome transplantation

Ear wound healing in MRL/MpJ mice is associated with gut microbiome composition and is transferable to non-healer mice via microbiome transplantation

The role of metabolomics in precision medicine of osteoarthritis: How far are we?

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