Dietary fatty acid content regulates wound repair and the pathogenesis of osteoarthritis following joint injury.
Dietary fatty acid content regulates wound repair and the pathogenesis of osteoarthritis following joint injury.
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DOI：
10.1136/annrheumdis-2014-205601
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发表时间：
2015-11
影响因子：
27.4
通讯作者：
Guilak F
中科院分区：
文献类型：
--
作者：
Wu CL;Jain D;McNeill JN;Little D;Anderson JA;Huebner JL;Kraus VB;Rodriguiz RM;Wetsel WC;Guilak F
肥胖和骨关节炎（OA）之间的联系机制尚不完全清楚，通常归因于体重增加，而不是代谢或炎症因素。在这里，我们研究了膳食脂肪酸、脂肪因子和体重对骨性关节炎小鼠模型关节损伤的影响。小鼠被喂食富含各种脂肪酸（FAs）的高脂肪饲料，包括饱和脂肪酸（SFAs）、ω-6多不饱和脂肪酸（PUFAs）和ω-3多不饱和脂肪酸。骨关节炎是通过破坏内侧半月板的稳定而引起的。用耳穿孔法评估伤口愈合情况。骨性关节炎，滑膜炎和伤口愈合的组织学检查，同时用显微ct测量骨变化。在不同时间点测量活性水平和血清细胞因子。采用多变量模型来阐明饮食、代谢和机械因素与OA和伤口愈合的关系。通过体重匹配小鼠和多变量模型，我们发现OA与膳食脂肪酸含量和血清脂肪因子水平显著相关，但与体重无关。此外，小鼠的自发活动与OA的发展无关。高脂肪饮食中少量ω-3 PUFAs（按千卡计算为8%）足以减轻损伤性OA，降低瘦素和抵抗素水平。ω-3 PUFAs显著增强伤口修复，sfa或ω-6 PUFAs单独增加OA严重程度、异位骨化和疤痕组织形成。我们的研究结果表明，膳食FA含量是OA严重程度和肥胖伤口再生的主要调节因子，支持进一步研究膳食FA补充剂作为OA潜在治疗方法的必要性。
The mechanisms linking obesity and osteoarthritis (OA) are not fully understood and have been generally attributed to increased weight, rather than metabolic or inflammatory factors. Here, we examined the influence of dietary fatty acids, adipokines, and body weight following joint injury in mouse model of OA. Mice were fed high-fat diets rich in various fatty acids (FAs) including saturated FAs (SFAs), ω-6 polyunsaturated FAs (PUFAs), and ω-3 PUFAs. OA was induced by destabilizing the medial meniscus. Wound healing was evaluated using an ear punch. OA, synovitis and wound healing were determined histologically, while bone changes were measured using microCT. Activity levels and serum cytokines were measured at various time-points. Multivariate models were performed to elucidate the associations of dietary, metabolic, and mechanical factors with OA and wound healing. Using weight-matched mice and multivariate models, we found that OA was significantly associated with dietary fatty acid content and serum adipokine levels, but not with body weight. Furthermore, spontaneous activity of the mice was independent of OA development. Small amounts of ω-3 PUFAs (8% by kcal) in a high-fat diet were sufficient to mitigate injury-induced OA, decreasing leptin and resistin levels. ω-3 PUFAs significantly enhanced wound repair, SFAs or ω-6 PUFAs independently increased OA severity, heterotopic ossification, and scar tissue formation. Our results indicate that dietary FA content is a primary regulator of OA severity and wound regeneration with obesity, supporting the need for further studies of dietary FA supplements as a potential therapeutic approach for OA.
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影响因子：
--
作者：
Louer, Craig R.;Furman, Bridgette D.;Huebner, Janet L.;Kraus, Virginia B.;Olson, Steven A.;Guilak, Farshid
通讯作者：
Guilak, Farshid
影响因子：
--
作者：
Griffin, Timothy M.;Huebner, Janet L.;Kraus, Virginia B.;Guilak, Farshid
通讯作者：
Guilak, Farshid
影响因子：
29
作者：
Kajimura D;Lee HW;Riley KJ;Arteaga-Solis E;Ferron M;Zhou B;Clarke CJ;Hannun YA;DePinho RA;Guo XE;Mann JJ;Karsenty G
通讯作者：
Karsenty G
影响因子：
7
作者：
Bakker, AC;van de Loo, FAJ;van den Berg, WB
通讯作者：
van den Berg, WB
DOI：
10.1073/pnas.0334211100
发表时间：
2003-02-18
影响因子：
11.1
作者：
Bagga, D;Wang, L;Reddy, ST
通讯作者：
Reddy, ST