Variable cartilage degradation in mice with diet-induced metabolic dysfunction: Food for thought

A. E. Kozijn; L. M. Gierman; F. van der Ham; P. Mulder; M. C. Morrison; S. Kuhnast; R. A. van der Heijden; P. M. Stavro; A. van Koppen; E. J. Pieterman; A. M. van den Hoek; R. Kleemann; H. M. G. Princen; S. C. Mastbergen; F. P. J. G. Lafeber; A. -M. Zuurmond; I. Bobeldijk; H. Weinans; R. Stoop

doi:10.1016/j.joca.2017.10.010

Variable cartilage degradation in mice with diet-induced metabolic dysfunction: Food for thought

A. E. Kozijn, L. M. Gierman, F. van der Ham, P. Mulder, M. C. Morrison, S. Kuhnast, R. A. van der Heijden, P. M. Stavro, A. van Koppen, E. J. Pieterman, A. M. van den Hoek, R. Kleemann, H. M. G. Princen, S. C. Mastbergen, F. P. J. G. Lafeber, A. -M. Zuurmond, I. Bobeldijk, H. Weinans, R. Stoop^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

21 Citations (Scopus)

Abstract

Objective: Human cohort studies have demonstrated a role for systemic metabolic dysfunction in osteoarthritis (OA) pathogenesis in obese patients. To explore the mechanisms underlying this metabolic phenotype of OA, we examined cartilage degradation in the knees of mice from different genetic backgrounds in which a metabolic phenotype was established by various dietary approaches.

Design: Wild-type C57BL/6J mice and genetically modified mice (hCRP, LDLr-/-. Leiden and ApoE*3Leiden. CETP mice) based on C57BL/6J background were used to investigate the contribution of inflammation and altered lipoprotein handling on diet-induced cartilage degradation. High-caloric diets of different macronutrient composition (i.e., high-carbohydrate or high-fat) were given in regimens of varying duration to induce a metabolic phenotype with aggravated cartilage degradation relative to controls.

Results: Metabolic phenotypes were confirmed in all studies as mice developed obesity, hypercholesteremia, glucose intolerance and/or insulin resistance. Aggravated cartilage degradation was only observed in two out of the twelve experimental setups, specifically in long-term studies in male hCRP and female ApoE*3Leiden. CETP mice. C57BL/6J and LDLr-/-. Leiden mice did not develop HFD-induced OA under the conditions studied. Osteophyte formation and synovitis scores showed variable results between studies, but also between strains and gender.

Conclusions: Long-term feeding of high-caloric diets consistently induced a metabolic phenotype in various C57BL/6J (-based) mouse strains. In contrast, the induction of articular cartilage degradation proved variable, which suggests that an additional trigger might be necessary to accelerate diet-induced OA progression. Gender and genetic modifications that result in a humanized pro-inflammatory state (human CRP) or lipoprotein metabolism (human-E3L. CETP) were identified as important contributing factors. (c) 2017 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.

Original language	English
Pages (from-to)	95-107
Number of pages	13
Journal	Osteoarthritis and cartilage
Volume	26
Issue number	1
DOIs	https://doi.org/10.1016/j.joca.2017.10.010
Publication status	Published - Jan-2018

Keywords

Osteoarthritis
Metabolic dysfunction
High-fat diet
Obesity
Mouse model
C-REACTIVE PROTEIN
HIGH-FAT DIET
KNEE OSTEOARTHRITIS
TRANSGENIC MICE
ATHEROSCLEROSIS DEVELOPMENT
TISSUE INFLAMMATION
INDUCED OBESITY
MOUSE MODELS
METAANALYSIS
PROGRESSION

Access to Document

10.1016/j.joca.2017.10.010

Handle.net

Persistent link

Embargoed Document

Variable cartilage degradation in mice with diet-induced metabolic dysfunction
Final publisher's version, 3.12 MB

Cite this

Kozijn, A. E., Gierman, L. M., van der Ham, F., Mulder, P., Morrison, M. C., Kuhnast, S., van der Heijden, R. A., Stavro, P. M., van Koppen, A., Pieterman, E. J., van den Hoek, A. M., Kleemann, R., Princen, H. M. G., Mastbergen, S. C., Lafeber, F. P. J. G., Zuurmond, A. -M., Bobeldijk, I., Weinans, H., & Stoop, R. (2018). Variable cartilage degradation in mice with diet-induced metabolic dysfunction: Food for thought. Osteoarthritis and cartilage, 26(1), 95-107. https://doi.org/10.1016/j.joca.2017.10.010

@article{5761d086e01446a1b99ad875ef54636c,

title = "Variable cartilage degradation in mice with diet-induced metabolic dysfunction: Food for thought",

abstract = "Objective: Human cohort studies have demonstrated a role for systemic metabolic dysfunction in osteoarthritis (OA) pathogenesis in obese patients. To explore the mechanisms underlying this metabolic phenotype of OA, we examined cartilage degradation in the knees of mice from different genetic backgrounds in which a metabolic phenotype was established by various dietary approaches.Design: Wild-type C57BL/6J mice and genetically modified mice (hCRP, LDLr-/-. Leiden and ApoE*3Leiden. CETP mice) based on C57BL/6J background were used to investigate the contribution of inflammation and altered lipoprotein handling on diet-induced cartilage degradation. High-caloric diets of different macronutrient composition (i.e., high-carbohydrate or high-fat) were given in regimens of varying duration to induce a metabolic phenotype with aggravated cartilage degradation relative to controls.Results: Metabolic phenotypes were confirmed in all studies as mice developed obesity, hypercholesteremia, glucose intolerance and/or insulin resistance. Aggravated cartilage degradation was only observed in two out of the twelve experimental setups, specifically in long-term studies in male hCRP and female ApoE*3Leiden. CETP mice. C57BL/6J and LDLr-/-. Leiden mice did not develop HFD-induced OA under the conditions studied. Osteophyte formation and synovitis scores showed variable results between studies, but also between strains and gender.Conclusions: Long-term feeding of high-caloric diets consistently induced a metabolic phenotype in various C57BL/6J (-based) mouse strains. In contrast, the induction of articular cartilage degradation proved variable, which suggests that an additional trigger might be necessary to accelerate diet-induced OA progression. Gender and genetic modifications that result in a humanized pro-inflammatory state (human CRP) or lipoprotein metabolism (human-E3L. CETP) were identified as important contributing factors. (c) 2017 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.",

keywords = "Osteoarthritis, Metabolic dysfunction, High-fat diet, Obesity, Mouse model, C-REACTIVE PROTEIN, HIGH-FAT DIET, KNEE OSTEOARTHRITIS, TRANSGENIC MICE, ATHEROSCLEROSIS DEVELOPMENT, TISSUE INFLAMMATION, INDUCED OBESITY, MOUSE MODELS, METAANALYSIS, PROGRESSION",

author = "Kozijn, {A. E.} and Gierman, {L. M.} and {van der Ham}, F. and P. Mulder and Morrison, {M. C.} and S. Kuhnast and {van der Heijden}, {R. A.} and Stavro, {P. M.} and {van Koppen}, A. and Pieterman, {E. J.} and {van den Hoek}, {A. M.} and R. Kleemann and Princen, {H. M. G.} and Mastbergen, {S. C.} and Lafeber, {F. P. J. G.} and Zuurmond, {A. -M.} and I. Bobeldijk and H. Weinans and R. Stoop",

year = "2018",

month = jan,

doi = "10.1016/j.joca.2017.10.010",

language = "English",

volume = "26",

pages = "95--107",

journal = "Osteoarthritis and cartilage",

issn = "1063-4584",

publisher = "ELSEVIER SCI LTD",

number = "1",

}

Kozijn, AE, Gierman, LM, van der Ham, F, Mulder, P, Morrison, MC, Kuhnast, S, van der Heijden, RA, Stavro, PM, van Koppen, A, Pieterman, EJ, van den Hoek, AM, Kleemann, R, Princen, HMG, Mastbergen, SC, Lafeber, FPJG, Zuurmond, A-M, Bobeldijk, I, Weinans, H & Stoop, R 2018, 'Variable cartilage degradation in mice with diet-induced metabolic dysfunction: Food for thought', Osteoarthritis and cartilage, vol. 26, no. 1, pp. 95-107. https://doi.org/10.1016/j.joca.2017.10.010

TY - JOUR

T1 - Variable cartilage degradation in mice with diet-induced metabolic dysfunction

T2 - Food for thought

AU - Kozijn, A. E.

AU - Gierman, L. M.

AU - van der Ham, F.

AU - Mulder, P.

AU - Morrison, M. C.

AU - Kuhnast, S.

AU - van der Heijden, R. A.

AU - Stavro, P. M.

AU - van Koppen, A.

AU - Pieterman, E. J.

AU - van den Hoek, A. M.

AU - Kleemann, R.

AU - Princen, H. M. G.

AU - Mastbergen, S. C.

AU - Lafeber, F. P. J. G.

AU - Zuurmond, A. -M.

AU - Bobeldijk, I.

AU - Weinans, H.

AU - Stoop, R.

PY - 2018/1

Y1 - 2018/1

N2 - Objective: Human cohort studies have demonstrated a role for systemic metabolic dysfunction in osteoarthritis (OA) pathogenesis in obese patients. To explore the mechanisms underlying this metabolic phenotype of OA, we examined cartilage degradation in the knees of mice from different genetic backgrounds in which a metabolic phenotype was established by various dietary approaches.Design: Wild-type C57BL/6J mice and genetically modified mice (hCRP, LDLr-/-. Leiden and ApoE*3Leiden. CETP mice) based on C57BL/6J background were used to investigate the contribution of inflammation and altered lipoprotein handling on diet-induced cartilage degradation. High-caloric diets of different macronutrient composition (i.e., high-carbohydrate or high-fat) were given in regimens of varying duration to induce a metabolic phenotype with aggravated cartilage degradation relative to controls.Results: Metabolic phenotypes were confirmed in all studies as mice developed obesity, hypercholesteremia, glucose intolerance and/or insulin resistance. Aggravated cartilage degradation was only observed in two out of the twelve experimental setups, specifically in long-term studies in male hCRP and female ApoE*3Leiden. CETP mice. C57BL/6J and LDLr-/-. Leiden mice did not develop HFD-induced OA under the conditions studied. Osteophyte formation and synovitis scores showed variable results between studies, but also between strains and gender.Conclusions: Long-term feeding of high-caloric diets consistently induced a metabolic phenotype in various C57BL/6J (-based) mouse strains. In contrast, the induction of articular cartilage degradation proved variable, which suggests that an additional trigger might be necessary to accelerate diet-induced OA progression. Gender and genetic modifications that result in a humanized pro-inflammatory state (human CRP) or lipoprotein metabolism (human-E3L. CETP) were identified as important contributing factors. (c) 2017 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.

AB - Objective: Human cohort studies have demonstrated a role for systemic metabolic dysfunction in osteoarthritis (OA) pathogenesis in obese patients. To explore the mechanisms underlying this metabolic phenotype of OA, we examined cartilage degradation in the knees of mice from different genetic backgrounds in which a metabolic phenotype was established by various dietary approaches.Design: Wild-type C57BL/6J mice and genetically modified mice (hCRP, LDLr-/-. Leiden and ApoE*3Leiden. CETP mice) based on C57BL/6J background were used to investigate the contribution of inflammation and altered lipoprotein handling on diet-induced cartilage degradation. High-caloric diets of different macronutrient composition (i.e., high-carbohydrate or high-fat) were given in regimens of varying duration to induce a metabolic phenotype with aggravated cartilage degradation relative to controls.Results: Metabolic phenotypes were confirmed in all studies as mice developed obesity, hypercholesteremia, glucose intolerance and/or insulin resistance. Aggravated cartilage degradation was only observed in two out of the twelve experimental setups, specifically in long-term studies in male hCRP and female ApoE*3Leiden. CETP mice. C57BL/6J and LDLr-/-. Leiden mice did not develop HFD-induced OA under the conditions studied. Osteophyte formation and synovitis scores showed variable results between studies, but also between strains and gender.Conclusions: Long-term feeding of high-caloric diets consistently induced a metabolic phenotype in various C57BL/6J (-based) mouse strains. In contrast, the induction of articular cartilage degradation proved variable, which suggests that an additional trigger might be necessary to accelerate diet-induced OA progression. Gender and genetic modifications that result in a humanized pro-inflammatory state (human CRP) or lipoprotein metabolism (human-E3L. CETP) were identified as important contributing factors. (c) 2017 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.

KW - Osteoarthritis

KW - Metabolic dysfunction

KW - High-fat diet

KW - Obesity

KW - Mouse model

KW - C-REACTIVE PROTEIN

KW - HIGH-FAT DIET

KW - KNEE OSTEOARTHRITIS

KW - TRANSGENIC MICE

KW - ATHEROSCLEROSIS DEVELOPMENT

KW - TISSUE INFLAMMATION

KW - INDUCED OBESITY

KW - MOUSE MODELS

KW - METAANALYSIS

KW - PROGRESSION

U2 - 10.1016/j.joca.2017.10.010

DO - 10.1016/j.joca.2017.10.010

M3 - Article

SN - 1063-4584

VL - 26

SP - 95

EP - 107

JO - Osteoarthritis and cartilage

JF - Osteoarthritis and cartilage

IS - 1

ER -