Native Collagen II Relieves Bone Impairment through Improving Inflammation and Oxidative Stress in Ageing db/db Mice

Molecules. 2021 Aug 15;26(16):4942. doi: 10.3390/molecules26164942.

Abstract

Ageing-related bone impairment due to exposure to hyperglycemic environment is scarcely researched. The aim was to confirm the improvement effects of undenatured type II collagen (UC II) on bone impairment in ageing db/db mice, and the ageing model was established by normal feeding for 48-week-old. Then, the ageing db/db mice were randomly assigned to UC II intervention, the ageing model, and the chondroitin sulfate + glucosamine hydrochloride control groups. After 12 weeks of treatment, femoral microarchitecture and biomechanical parameters were observed, biomarkers including bone metabolism, inflammatory cytokines, and oxidative stress were measured, and the gastrocnemius function and expressions of interleukin (IL) 1β, receptor activator of nuclear factor (NF)-κB ligand (RANKL), and tartrate-resistant acid phosphatase (TRAP) were analyzed. The results showed that the mice in the UC II intervention group showed significantly superior bone and gastrocnemius properties than those in the ageing model group, including bone mineral density (287.65 ± 72.77 vs. 186.97 ± 32.2 mg/cm3), gastrocnemius index (0.46 ± 0.07 vs. 0.18 ± 0.01%), muscle fiber diameter (0.0415 ± 0.005 vs. 0.0330 ± 0.002 mm), and cross-sectional area (0.0011 ± 0.00007 vs. 0.00038 ± 0.00004 mm2). The UC II intervention elevated bone mineralization and formation and decreased bone resorption, inflammatory cytokines, and the oxidative stress. In addition, lower protein expression of IL-1β, RANKL, and TRAP in the UC II intervention group was observed. These findings suggested that UC II improved bones impaired by T2DM during ageing, and the likely mechanism was partly due to inhibition of inflammation and oxidative stress.

Keywords: T2DM; bone impairment; db/db mice; inflammation; oxidative stress; undenatured type II collagen (UC II).

MeSH terms

  • Aging / drug effects
  • Aging / genetics
  • Aging / pathology
  • Animals
  • Bone Density / drug effects
  • Bone Resorption / drug therapy*
  • Bone Resorption / etiology
  • Bone Resorption / genetics
  • Bone Resorption / pathology
  • Chondroitin Sulfates / pharmacology
  • Collagen Type II / pharmacology*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / pathology
  • Gene Expression Regulation / drug effects
  • Glucosamine / pharmacology
  • Humans
  • Inflammation / drug therapy
  • Inflammation / etiology
  • Inflammation / genetics
  • Inflammation / pathology
  • Interleukin-1beta / genetics*
  • Mice
  • Mice, Inbred NOD / genetics
  • Oxidative Stress / drug effects
  • RANK Ligand / genetics*
  • Tartrate-Resistant Acid Phosphatase / genetics*

Substances

  • Collagen Type II
  • IL1B protein, mouse
  • Interleukin-1beta
  • RANK Ligand
  • Tnfsf11 protein, mouse
  • Chondroitin Sulfates
  • Acp5 protein, mouse
  • Tartrate-Resistant Acid Phosphatase
  • Glucosamine