Initial responses of articular tissues in a murine high-fat diet-induced osteoarthritis model: pivotal role of the IPFP as a cytokine fountain.
Initial responses of articular tissues in a murine high-fat diet-induced osteoarthritis model: pivotal role of the IPFP as a cytokine fountain.
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DOI：
10.1371/journal.pone.0060706
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Asou Y
中科院分区：
文献类型：
--
作者：
Iwata M;Ochi H;Hara Y;Tagawa M;Koga D;Okawa A;Asou Y
肥胖和高体重指数与骨关节炎（OA）的发病率较高相关。本研究的目的是调查髌下脂肪垫（IPFP）在高脂饮食（HFD）对膝关节OA发展的亚急性影响中的参与。C57 BL/6 J雄性小鼠从7周龄开始喂食HFD或正常饮食。用免疫组织化学分析评价组织切片。切除IPFP，并使用实时RT-PCR分析比较mRNA表达谱。HFD组在HFD 8周后开始出现骨关节炎变化。在骨赘形成之前，胫骨平台前缘的滑膜细胞数量和血管生成增加。定量组织学分析表明，8周后HFD组的骨赘体积显著增加，IPFP体积、单个脂肪细胞的大小和IPFP中血管的数量沿着增加。组织形态计量学分析显示骨赘面积与IPFP面积、单个脂肪细胞面积和血管面积显著相关。实时RT-PCR分析显示，HFD 8周后，IPFP中炎性细胞因子、生长因子和脂肪因子的mRNA表达升高。这些发现与HFD 8周后CD 68巨噬细胞标志物的表达增加平行。脂肪因子的表达水平与TNF-α、VEGF和TGF-β的表达水平显著相关。免疫组化分析显示，Nampt蛋白在IPFP中高度表达，尤其是在骨赘形成部位周围。骨赘形成部位软骨细胞的凋亡和增殖均增强，表明该区域的细胞更新率较高。这些观察结果表明，IPFP在骨赘的形成中起着关键作用，并作为一个分泌器官响应于HFD。
Obesity and high body mass index are associated with a higher incidence of osteoarthritis (OA). The aim of this study is to investigate the involvement of the infrapatellar fat pad (IPFP) in the sub-acute effect of a high fat diet (HFD) on the development of knee-OA. C57BL/6J male mice were fed either a HFD or a normal diet beginning at seven weeks of age. Tissue sections were evaluated with immunohistological analysis. The IPFP was excised, and mRNA expression profiles were compared using real-time RT-PCR analysis. Osteoarthritic changes were initiated in the HFD group after eight weeks of the HFD. Increased synovial cell number and angiogenesis at the anterior edge of the tibial plateau were exhibited prior to osteophyte formation. Quantitative histological analysis indicated that osteophyte volume was significantly increased in the HFD group after eight weeks, along with an increase in the IPFP volume, the size of individual adipocytes and the number of vessels in the IPFP. Histomorphometrical analysis revealed osteophyte area was significantly associated with IPFP area, individual adipocyte area and vascular area. Real-time RT-PCR analysis demonstrated elevated mRNA expression of inflammatory cytokines, growth factor, and adipokines in the IPFP after eight weeks of the HFD. These findings are in parallel with increased expression of the CD68 macrophage marker after eight weeks of the HFD. Expression levels of the adipokines were significantly correlated with expression of TNF-α, VEGF and TGF-β. Immunohistological analysis revealed that the Nampt protein was highly expressed in the IPFP especially around the site of osteophyte formation. Apoptosis and proliferation of chondrocytes were both enhanced at the site of osteophyte formation, indicating higher cell turnover at this region. These observations suggest the IPFP plays a pivotal role in the formation of osteophytes and functions as a secretory organ in response to a HFD.
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DOI：
10.1258/mi.2008.008018
发表时间：
2008-12-01
期刊：
Menopause international
影响因子：
--
作者：
Magliano, Malgorzata
通讯作者：
Magliano, Malgorzata
影响因子：
3.9
作者：
Laurberg, Trine Bay;Frystyk, Jan;Stengaard-Pedersen, Kristian
通讯作者：
Stengaard-Pedersen, Kristian
影响因子：
27.4
作者：
Dahaghin, S.;Bierma-Zeinstra, S. M. A.;Pols, H. A. P.
通讯作者：
Pols, H. A. P.
影响因子：
7.7
作者：
Honsawek, Sittisak;Chayanupatkul, Maneerat
通讯作者：
Chayanupatkul, Maneerat
DOI：
10.1038/ncpendmet0976
发表时间：
2008-11
期刊：
NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM
影响因子：
--
作者：
Odegaard, Justin I.;Chawla, Ajay
通讯作者：
Chawla, Ajay