Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis.
Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis.
复制标题
DOI：
10.1002/art.24854
复制
发表时间：
2009-10
影响因子：
--
通讯作者：
Guilak, Farshid
中科院分区：
文献类型：
--
作者：
Griffin, Timothy M.;Huebner, Janet L.;Kraus, Virginia B.;Guilak, Farshid
验证瘦素基因或瘦素受体基因缺失导致的肥胖导致膝关节骨关节炎、全身炎症和软骨下骨形态改变增加的假设。我们研究了瘦素缺乏（ob/ob）和瘦素受体缺乏（db/db）的雌性小鼠与野生型动物相比，通过组织病理学记录膝关节骨关节炎。使用多重珠免疫测定法测量血清促炎细胞因子和抗炎细胞因子。皮质和松质骨软骨下骨的变化记录了微型计算机断层扫描，和身体成分进行了定量的双能X线吸收。与对照组相比，肥胖症在ob/ob和db/db小鼠中增加了约10倍，但与膝关节骨关节炎的发病率增加无关。与对照组相比，ob/ob和db/db小鼠的血清细胞因子水平也没有变化，但KC（白细胞介素8的鼠类似物）除外，其升高。瘦素损伤与胫骨骨骺软骨下骨厚度减少和相对骨小梁体积增加有关。由于瘦素信号传导受损导致的极度肥胖诱导了软骨下骨形态学的改变，而没有增加膝关节骨关节炎的发病率。在ob/ob和db/db小鼠中，全身炎性细胞因子水平基本保持不变。这些发现表明，体脂本身可能不是关节退行性变的风险因素，因为在缺乏瘦素信号传导的情况下，肥胖不足以诱导雌性C57 BL/6 J小鼠的全身炎症和膝关节骨关节炎。这些结果表明瘦素通过调节骨骼和免疫系统在骨关节炎的发展中发挥多效性作用。
To test the hypothesis that obesity resulting from deletion of the leptin gene or leptin receptor gene results in increased knee osteoarthritis, systemic inflammation, and altered subchondral bone morphology. We studied leptin deficient (ob/ob) and leptin receptor deficient (db/db) female mice compared to wild-type animals to document knee osteoarthritis via histopathology. Serum pro- and anti-inflammatory cytokines were measured using a multiplex bead immunoassay. Cortical and trabecular subchondral bone changes were documented by micro-computed tomography, and body composition was quantified by dual-energy X-ray absorptiometry. Adiposity was increased by approximately 10-fold in ob/ob and db/db mice compared to controls, but it was not associated with increased incidence of knee osteoarthritis. Serum cytokine levels also were unchanged in ob/ob and db/db mice relative to controls, except for KC (murine analog of interleukin 8), which was elevated. Leptin impairment was associated with reduced subchondral bone thickness and increased relative trabecular bone volume in the tibial epiphysis. Extreme obesity due to impaired leptin signaling induced alterations in subchondral bone morphology without increased incidence of knee osteoarthritis. Systemic inflammatory cytokine levels remained largely unchanged in ob/ob and db/db mice. These findings suggest that body fat, in and of itself, may not be a risk factor for joint degeneration as adiposity in the absence of leptin signaling is insufficient to induce systemic inflammation and knee osteoarthritis in female C57BL/6J mice. The results imply a pleiotropic role for leptin in the development of osteoarthritis by regulating both the skeletal and immune systems.
登录
查看更多内容
DOI：
10.1097/00005768-199911001-00008
发表时间：
1999-11-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
Jebb, SA;Moore, MS
通讯作者：
Moore, MS
影响因子：
4.1
作者：
Kishida, Y;Hirao, M;Myoui, A
通讯作者：
Myoui, A
影响因子：
56.9
作者：
Chehab, FF;Mounzih, K;Lim, ME
通讯作者：
Lim, ME
影响因子：
4.1
作者：
Hamrick, MW;Pennington, C;Isales, C
通讯作者：
Isales, C
影响因子：
6.9
作者：
Ahima, Rexford S.
通讯作者：
Ahima, Rexford S.