Genistein Suppresses IL-6 and MMP-13 to Attenuate Osteoarthritis in Obese Diabetic Mice

被引:7
作者
Lopez, Janelle [1 ]
Al-Nakkash, Layla [2 ]
Broderick, Tom L. [3 ]
Castro, Monica [4 ]
Tobin, Brielle [1 ]
Plochocki, Jeffrey H. [4 ,5 ]
机构
[1] Midwestern Univ, Arizona Coll Osteopath Med, Glendale, AZ 85308 USA
[2] Midwestern Univ, Coll Grad Studies, Dept Physiol, Glendale, AZ 85308 USA
[3] Midwestern Univ, Coll Grad Studies, Dept Physiol, Lab Diabet & Exercise Metab, Glendale, AZ 85308 USA
[4] Midwestern Univ, Coll Grad Studies, Dept Anat, Glendale, AZ 85308 USA
[5] Univ Cent Florida, Coll Med, Orlando, FL 32827 USA
关键词
obesity; type; 2; diabetes; osteoarthritis; genistein; exercise; MELLITUS; CARTILAGE; EXERCISE;
D O I
10.3390/metabo13091014
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Type 2 diabetes mellitus and osteoarthritis (OA) often present as comorbidities. We examined the role of plasma IL-6, chondrocyte MMP-13, and col10a expression in the development of OA in obese diabetic mice. We further investigated dietary genistein and exercise training as potential mitigators of OA. One hundred adult mice (50 females, 50 males) aged 6 weeks were randomized into 5 groups, including lean controls, obese diabetic controls, and obese diabetic mice treated with genistein, exercise training, and genistein plus exercise training. The obese diabetic state was induced by feeding the mice a high-fat, high-sugar diet. Genistein was incorporated into the diet at a concentration of 600 mg genistein/kg. Exercise training was performed on a treadmill and consisted of daily 30 min sessions at 12 m/min, 5 days/week for a 12-week period. After treatment, plasma was collected, and proximal tibias were removed for analysis. Plasma IL-6 and MMP-13 were elevated while col10a was reduced in obese diabetic mice in comparison to lean controls. Dietary genistein treatment reduced IL-6 and MMP-13 expression and increased col10a expression. Histological examination of articular cartilage showed reduced thickness of the uncalcified zones and proteoglycan content in the cartilage of diabetic mice in comparison to mice fed genistein. Exercise training had no significant effect. In conclusion, genistein (and not exercise training) attenuates OA by reducing IL-6 and MMP-13 expression in diabetic mice.
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页数:9
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共 39 条
  • [1] IL-6 signalling pathways and the development of type 2 diabetes
    Akbari, Mohamad
    Hassan-Zadeh, Vahideh
    [J]. INFLAMMOPHARMACOLOGY, 2018, 26 (03) : 685 - 698
  • [2] Genistein: A promising therapeutic agent for obesity and diabetes treatment
    Behloul, Nouredine
    Wu, Guanzhong
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 2013, 698 (1-3) : 31 - 38
  • [3] High-fat, high-sugar diet induces splenomegaly that is ameliorated with exercise and genistein treatment
    Buchan L.
    St Aubin C.R.
    Fisher A.L.
    Hellings A.
    Castro M.
    Al-Nakkash L.
    Broderick T.L.
    Plochocki J.H.
    [J]. BMC Research Notes, 11 (1)
  • [4] The Phenotypic Approach to Osteoarthritis: A Look at Metabolic Syndrome-Associated Osteoarthritis
    Courties, Alice
    Berenbaum, Francis
    Sellam, Jeremie
    [J]. JOINT BONE SPINE, 2019, 86 (06) : 725 - 730
  • [5] Di Rosa Michelino, 2019, J Funct Morphol Kinesiol, V4, DOI 10.3390/jfmk4010011
  • [6] Estrogen receptor impairs interleukin-6 expression by preventing protein binding on the NF-kappa B site
    Galien, R
    Garcia, T
    [J]. NUCLEIC ACIDS RESEARCH, 1997, 25 (12) : 2424 - 2429
  • [7] The effect of graded exercise on IL-6 release and glucose uptake in human skeletal muscle
    Helge, JW
    Stallknecht, B
    Pedersen, BK
    Galbo, H
    Kiens, B
    Richter, EA
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 2003, 546 (01): : 299 - 305
  • [8] Bone Strength Is Improved with Genistein Treatment in Mice with Diet-Induced Obesity
    Hellings, Austin
    Buchan, Levi
    Castro, Monica
    St Aubin, Chaheyla R.
    Fisher, Amy L.
    Al-Nakkash, Layla
    Broderick, Tom L.
    Plochocki, Jeffrey H.
    [J]. CURRENT DEVELOPMENTS IN NUTRITION, 2019, 3 (11):
  • [9] Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis
    Hu, Qichan
    Ecker, Melanie
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (04) : 1 - 22
  • [10] Veterans With Diabetes Receive Arthroplasty More Frequently and at a Younger Age
    King, Karen B.
    Findley, Thomas W.
    Williams, Allison E.
    Bucknell, Allan L.
    [J]. CLINICAL ORTHOPAEDICS AND RELATED RESEARCH, 2013, 471 (09) : 3049 - 3054