Effect of obesity induced by high-fat diet and adipose exosomes on knee post-traumatic osteoarthritis caused by destabilization of medial meniscus surgery in young mice
10.16438/j.0513-4870.2023-0036
- VernacularTitle:高脂饮食诱导的肥胖及其脂肪细胞外泌体对年轻小鼠创伤性膝关节炎的影响及机制研究
- Author:
Li-tong WU
1
;
Bao-chao LI
2
;
Bo YAO
1
;
Zi-chun HUA
3
Author Information
1. Nanjing Foreign Language School, Nanjing 210008, China
2. Nanjing Stomatological Hospital, Affiliated Stomatological Hospital, Medical School, Nanjing University, Nanjing 210019, China
3. School of Life Sciences, Nanjing University, Nanjing 210023, China; Jiangsu Society of Biochemistry and Molecular Biology and Nanjing Genrecom Laboratories, Ltd., Nanjing 211899, China
- Publication Type:Research Article
- Keywords:
high-fat diet;
obesity;
adipose tissue;
exosome;
post-traumatic knee osteoarthritis
- From:
Acta Pharmaceutica Sinica
2023;58(8):2415-2423
- CountryChina
- Language:Chinese
-
Abstract:
Obesity is an important risk factor related to osteoarthritis, but it′s role in post-traumatic osteoarthritis on young people need to further study. The internal mechanism except the mechanical loading may be associated with adipose exosomes. To examine the effect of obesity induced by high fat diet and adipose exosomes on knee post-traumatic osteoarthritis caused by destabilization of medial meniscus (DMM) surgery in young mice, 20 6-week-old C57BL/6J mice were randomly assigned to the control diet group (CD, n = 5), the DMM group (n = 5), the high fat diet group (HFD, n = 5) and the HFD plus DMM group (HFD+DMM, n = 5). The CD and DMM group were fed with a control diet, and the HFD and HFD+DMM group were fed with a high fat diet. We did the DMM surgery and the sham surgery on the mice when it was 10 weeks old. Extract obese and normal adipose exosomes, identify exosomes in vitro, and proceed fluorescence imaging in vivo using DiR staining. DMM+HFD-Exo group and DMM+CD-Exo group were injected the exosomes from the tail vain once a week (100 μL per shot with a concentration of 1 μg·μL-1). Second, 15 6-week-old C57BL/6J mice were randomly assigned to the DMM group (n = 5), the DMM plus obese adipose exosomes group (DMM+HFD-Exo, n = 5), and the DMM plus control diet adipose exosomes group (DMM+CD-Exo, n = 5). Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Nanjing University (IACUC-D2204005). All mice were sacrificed at the age of 18 weeks, the knee joints of the mice were harvested and fixed. We used micro CT to examine the samples and measured the bone volume/tissue volume, trabecular thickness, trabecular number and trabecular separation. Then the samples were decalcified and embedded in paraffin, and 4 μm thickness sections were stained with H&E and safranin O/fast green to observe the histological changes of the knee joint. The results showed compared with the control diet group, high fat diet induced obesity can aggravate the pathological changes of the post-traumatic osteoarthritis caused by DMM surgery, which shows in having a higher Mankin score. The surface of knee articular cartilage in the HFD+DMM group was rough, and the subchondral bone has an increase in bone sclerosis. Compared with the DMM group, obese adipose exosomes can exacerbate the pathological changes of the knee articular cartilage, while not influencing the subchondral bone. In conclusion, high fat diet induced obesity can aggravate the post-traumatic osteoarthritis caused by DMM surgery in young mice. The obese adipose exosomes mainly affect the surface of the knee articular cartilage.
