ArticleBone2020
Aberrant structure of fibrillar collagen and elevated levels of advanced glycation end products typify delayed fracture healing in the diet-induced obesity mouse model.
Article in Bone, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Bone health in diabetes mellitus.Reviews in endocrine & metabolic disorders · 2026Review
- Novel image registration approach for combining 2D Osterix and collagen bundles images with 3D micro-CT.JBMR plus · 2026Article
- Article
- Comparison of the effects of hydrogel and normal saline as carriers of MSC on fracture healing in a rat long bone fracture model.Journal of orthopaedic surgery and research · 2025Article
- Skeletal stem and progenitor cells in bone physiology, ageing and disease.Nature reviews. Endocrinology · 2025Review
- Fortified Withaferin A accelerates the transition from fibrovascular to bone remodeling phase during endochondral bone formation to promote ossification.Frontiers in endocrinology · 2025Article
- Increased neutrophil extracellular traps caused by diet-induced obesity delay fracture healing.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Advanced glycation end products mediate biomineralization disorder in diabetic bone disease.Cell reports. Medicine · 2024Article
- Article
- Advantages and Limitations of Diabetic Bone Healing in Mouse Models: A Narrative Review.Biomedicines · 2023Review
- Cannabidiol and Cannabigerol, Nonpsychotropic Cannabinoids, as Analgesics that Effectively Manage Bone Fracture Pain and Promote Healing in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Article
- Exploring the Paradox of Bone Mineral Density in Type 2 Diabetes: A Comparative Study Using Opportunistic Chest CT Texture Analysis and DXA.Diagnostics (Basel, Switzerland) · 2023Article
- Bone and the Unfolded Protein Response: In Sickness and in Health.Calcified tissue international · 2023Review
- The Chemistry and Biology of Collagen Hybridization.Journal of the American Chemical Society · 2023Review
- The role of PIEZO ion channels in the musculoskeletal system.American journal of physiology. Cell physiology · 2023Review
- Distinct defects in early innate and late adaptive immune responses typify impaired fracture healing in diet-induced obesity.Frontiers in immunology · 2023Article
- Assessment of Bone Fracture Healing Using Micro-Computed Tomography.Journal of visualized experiments : JoVE · 2022Article
- Contrasting effects ofeLife · 2022Article
- The Effect of Obesity on Pediatric Tibia Fractures.The Iowa orthopaedic journal · 2022Article
- Structural changes in the collagen network of joint tissues in late stages of murine OA.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Impaired fracture healing in patients with obesity-associated type 2 diabetes (T2D) is a significant unmet clinical problem that affects millions of people worldwide. However, the underlying causes are poorly understood. Additionally, limited clinical information is available on how pre-diabetic hyperglycemia in obese individuals impacts bone healing. Here, we use the diet-induced obesity (DIO) mouse (C57BL/6J) model to study the impact of obesity-associated pre-diabetic hyperglycemia on bone healing and fibrillar collagen organization as healing proceeds from one phase to another. We show that DIO mice exhibit defective healing characterized by reduced bone mineral density, bone volume, and bone volume density. Differences in the healing pattern between lean and DIO mice occur early in the healing process as evidenced by faster resorption of the fibrocartilaginous callus in DIO mice. However, the major differences between lean and DIO mice occur during the later phases of endochondral ossification and bone remodeling. Comprehensive analyses of fibrillar collagen microstructure and expression pattern during these phases, using a set of complementary techniques that include histomorphometry, immunofluorescence staining, and second harmonic generation microscopy, demonstrate significant defects in DIO mice. Defects include strikingly sparse and disorganized collagen fibers, as well as pathological accumulation of unfolded collagen triple helices. We also demonstrate that DIO-associated changes in fibrillar collagen structure are attributable, at least in part, to the accumulation of advanced glycation end products, which increase the collagen-fiber crosslink density. These major changes impair fibrillar collagens functions, culminating in defective callus mineralization, remodeling, and strength. Our data extend the understanding of mechanisms by which obesity and its associated hyperglycemia impair fracture healing and underline defective fibrillar collagen microstructure as a novel and important contributor.
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