Obesity impairs revascularization and bone healing in a mouse model of osteonecrosis.
Zhuo DengMaria Aguirre-FloresHarry K W KimYinshi RenPublished in: Journal of orthopaedic research : official publication of the Orthopaedic Research Society (2023)
Osteonecrosis of the femoral head (ONFH) is a devastating bone disease that is caused by a disruption of blood supply leading to necrotic cell death. Clinically, it was found that obesity has a high prevalence with ONFH. However, it remains unclear how obesity may directly affect tissue regeneration and bone healing in osteonecrosis (ON). The purpose of this study is to investigate the effects of obesity and weight loss (WL) on ON healing. In this study, we induced obesity and WL in an established surgery-induced ON mouse model via feeding a high-fat diet (HFD) and altering the diet respectively. All mice received a surgical induction of ON of distal femoral epiphysis at the age of 12 weeks. HFD was switched to normal diet (ND) after ON surgery to induce WL. Mouse body weight was recorded weekly. Mouse body composition was scanned by DEXA (Dual-energy X-ray absorptiometry) right after sacrifice at the age of 16 weeks. The distal femoral bone samples were fixed and embedded for histology such as H&E, immunohistochemistry, and TRAP staining. In this study, we found that HFD-induced obesity impaired revascularization and bone remodeling showing decreased vessel areas and reduced osteoblast and osteoclast numbers. WL could rescue obesity-induced bone healing defects. Our study is the first to test the direct effects of obesity and WL on ON bone healing. We believe our work may provide new concepts for osteonecrosis treatment in obese patients. This article is protected by copyright. All rights reserved.
Keyphrases
- weight loss
- insulin resistance
- high fat diet
- bone mineral density
- high fat diet induced
- bariatric surgery
- metabolic syndrome
- body composition
- roux en y gastric bypass
- type diabetes
- weight gain
- mouse model
- gastric bypass
- obese patients
- minimally invasive
- cell death
- postmenopausal women
- dual energy
- soft tissue
- high glucose
- bone regeneration
- stem cells
- skeletal muscle
- coronary artery disease
- physical activity
- coronary artery bypass
- magnetic resonance imaging
- coronary artery bypass grafting
- high resolution
- atrial fibrillation
- cell proliferation
- pi k akt
- surgical site infection