ArticleJCI insight2019
Lowering circulating apolipoprotein E levels improves aged bone fracture healing.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Alzheimer's Disease Risk Factor APOE4 Exerts Dimorphic Effects on Female Bone.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Neutralizing hepatic apolipoprotein E enhances aged bone fracture healing.Bone research · 2026Article
- Using RNA therapeutics to promote healthy aging.Nature aging · 2025Review
- Insufficient Mechanical Loading Downregulates Piezo1 in Chondrocytes and Impairs Fracture Healing Through ApoE-Induced Senescence.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The impact of age and sex on the inflammatory response during bone fracture healing.JBMR plus · 2024Article
- Modulation of Bone Mineral Density and Its Response to Menopausal Hormone Therapy according to the Apolipoprotein E Genotype in Postmenopausal Korean Women.Journal of menopausal medicine · 2024Article
- Alzheimer's Disease and Impaired Bone Microarchitecture, Regeneration and Potential Genetic Links.Life (Basel, Switzerland) · 2023Review
- The role of Meteorin-like in skeletal development and bone fracture healing.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2022Article
- Low-intensity pulsed ultrasound/nanomechanical force generators enhance osteogenesis of BMSCs through microfilaments and TRPM7.Journal of nanobiotechnology · 2022Article
- Interleukin-13 Affects the Recovery Processes in a Mouse Model of Hemorrhagic Stroke with Bilateral Tibial Fracture.Molecular neurobiology · 2022Article
- Bone targeting nanocarrier-assisted delivery of adenosine to combat osteoporotic bone loss.Biomaterials · 2021Article
- Parabiosis: Assessing the Effects of Circulating Cells and Factors on the Skeleton.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Comparative proteomic analysis of osteogenic differentiated human adipose tissue and bone marrow-derived stromal cells.Journal of cellular and molecular medicine · 2020Article
- Maresin 1 resolves aged-associated macrophage inflammation to improve bone regeneration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Transcriptomic Changes Related to Cellular Processes with Particular Emphasis on Cell Activation in Lysosomal Storage Diseases from the Group of Mucopolysaccharidoses.International journal of molecular sciences · 2020Article
- Gukang Capsule Promotes Fracture Healing by Activating BMP/SMAD and Wnt/Evidence-based complementary and alternative medicine : eCAM · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Age is a well-established risk factor for impaired bone fracture healing. Here, we identify a role for apolipoprotein E (ApoE) in age-associated impairment of bone fracture healing and osteoblast differentiation, and we investigate the mechanism by which ApoE alters these processes. We identified that, in both humans and mice, circulating ApoE levels increase with age. We assessed bone healing in WT and ApoE-/- mice after performing tibial fracture surgery: bone deposition was higher within fracture calluses from ApoE-/- mice. In vitro recombinant ApoE (rApoE) treatment of differentiating osteoblasts decreased cellular differentiation and matrix mineralization. Moreover, this rApoE treatment decreased osteoblast glycolytic activity while increasing lipid uptake and fatty acid oxidation. Using parabiosis models, we determined that circulating ApoE plays a strong inhibitory role in bone repair. Using an adeno-associated virus-based siRNA system, we decreased circulating ApoE levels in 24-month-old mice and demonstrated that, as a result, fracture calluses from these aged mice displayed enhanced bone deposition and mechanical strength. Our results demonstrate that circulating ApoE as an aging factor inhibits bone fracture healing by altering osteoblast metabolism, thereby identifying ApoE as a new therapeutic target for improving bone repair in the elderly.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.