Abstract

Ageing-related bone impairment due to exposure to hyperglycemic environment is scarcely researched. The aim was to confirm the improvement effects of Native Collagen 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 Native Collagen 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 Native Collagen 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 Native Collagen 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 Native Collagen II intervention group was observed. These findings suggested that Native Collagen II improved bones impaired by T2DM during ageing, and the likely mechanism was partly due to inhibition of inflammation and oxidative stress.

Highlights

  • Diabetes mellitus (DM), caused by dysfunctional glucose metabolism, is a chronic endocrine disorder

  • In order to discover effective preventive measures for bone impairment in ageing coupled with Type 2 DM (T2DM), undenatured type II collagen (UC II) was administered in the ageing db/db mice during a period of 3 months

  • In order to explore the likely mechanism of action of UC II, the T2DM disease status, biomarkers, and the gastrocnemius function were analyzed

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Summary

Introduction

Diabetes mellitus (DM), caused by dysfunctional glucose metabolism, is a chronic endocrine disorder. Type 2 DM (T2DM) is a multifactorial disease, the central pathomechanisms of which are hyperinsulinemia, insulin resistance, and chronic inflammation, and progressive secondary β-cell failure occurs at the later stages [1,2]. With the increasing duration of DM, patients suffer from the complications including retinopathy, nephropathy, neuropathy, and vascular disease. Bone damage is known as a complication of DM [6], which is associated with significant morbidity, mortality, and reduction in quality of life [7]. The development of effective management of promoting early intervention and prevention of bone degeneration to improve the quality of life among elderly T2DM patients is needed

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