Griffin Timothy M, Guilak Farshid
Department of Surgery and Biomedical Engineering, Duke University Medical Center, Durham, NC 27710, USA.
Biorheology. 2008;45(3-4):387-98.
Obesity is one of the most significant, and potentially most preventable, risk factors for the development of osteoarthritis, and numerous studies have shown a strong association between body mass index and osteoarthritis of the hip, knee, foot and hand. However, the mechanism(s) by which obesity contributes to the onset and progression of osteoarthritis are not fully understood. The strong association between body mass index, altered limb alignment, and osteoarthritis of the knee--and the protective effects of weight loss--support the classic hypothesis that the effects of obesity on the joint are due to increased biomechanical loading and associated alterations in gait. However, obesity is now considered to be a low-grade systemic inflammatory disease, and recent studies suggest that metabolic factors associated with obesity alter systemic levels of pro-inflammatory cytokines that are also associated with osteoarthritis. Thus, the ultimate influence of obesity on osteoarthritis may involve a complex interaction of genetic, metabolic, and biomechanical factors. In this respect, mouse models of obesity can provide excellent systems in which to examine causal relationships among these factors. In recent years, there have been surprisingly few reports examining the effects of obesity on osteoarthritis using mouse models. In this paper, we review studies on mice and other animal models that provide both direct and indirect evidence on the role of obesity and altered diet in the development of osteoarthritis. We also examine the use of different body mass indices for characterizing "obesity" in mice by comparing these indices to typical adiposity levels observed in obese humans. Taken together, evidence from studies using mice suggest that a complex interaction of environmental and genetic factors associated with obesity contribute to the incidence and severity of osteoarthritis. The ability to control these factors, together with the development of methods to conduct more intricate measures of local biomechanical factors, make mouse models an excellent system to study obesity and osteoarthritis.
肥胖是骨关节炎发展过程中最重要且可能最可预防的风险因素之一，众多研究表明体重指数与髋、膝、足和手部骨关节炎之间存在密切关联。然而，肥胖导致骨关节炎发病和进展的机制尚未完全明确。体重指数、肢体对线改变与膝关节骨关节炎之间的密切关联，以及体重减轻的保护作用，支持了经典假说，即肥胖对关节的影响是由于生物力学负荷增加以及步态相关改变所致。然而，肥胖现在被认为是一种低度全身性炎症性疾病，最近的研究表明，与肥胖相关的代谢因素会改变全身促炎细胞因子水平，而这些细胞因子也与骨关节炎有关。因此，肥胖对骨关节炎的最终影响可能涉及遗传、代谢和生物力学因素的复杂相互作用。在这方面，肥胖小鼠模型可以提供极佳的系统来研究这些因素之间的因果关系。近年来，令人惊讶的是，使用小鼠模型研究肥胖对骨关节炎影响的报道极少。在本文中，我们综述了关于小鼠和其他动物模型的研究，这些研究为肥胖和饮食改变在骨关节炎发展中的作用提供了直接和间接证据。我们还通过将不同体重指数与肥胖人类中观察到的典型肥胖水平进行比较，研究了使用不同体重指数来表征小鼠“肥胖”的情况。综合来看，来自小鼠研究的证据表明，与肥胖相关的环境和遗传因素的复杂相互作用会导致骨关节炎的发生率和严重程度。能够控制这些因素，以及开发出更精确测量局部生物力学因素的方法，使得小鼠模型成为研究肥胖和骨关节炎的极佳系统。
