ArticleExperimental and therapeutic medicine2015
Rapamycin-induced autophagy activity promotes bone fracture healing in rats.
Article in Experimental and therapeutic medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Small-molecule autophagy modulators: Mechanisms, therapeutic potential, and development challenges in pathological settings.Fundamental research · 2026Review
- Rapamycin reduces peritendinous fibrosis but has a limited effect on intratendinous healing in a rodent Achilles tendon injury model.Scientific reports · 2026Article
- Article
- Rapamycin does not alter bone microarchitecture or material properties quality in young-adult and aged female C57BL/6 mice.JBMR plus · 2024Article
- The Effect of a Local Injection of Flurbiprofen Ester Microspheres on Systemic Inflammatory Model Rats With a Closed Femoral Shaft Fracture.Frontiers in pharmacology · 2022Article
- Autophagy: An important target for natural products in the treatment of bone metabolic diseases.Frontiers in pharmacology · 2022Review
- Cartilage-targeting peptide-modified dual-drug delivery nanoplatform with NIR laser response for osteoarthritis therapy.Bioactive materials · 2021Article
- Histological Evaluation and Gene Expression Profiling of Autophagy-Related Genes for Cartilage of Young and Senescent Rats.International journal of molecular sciences · 2020Article
- Protective Effect of Curcumin on Bone Trauma in a Rat Model via Expansion of Myeloid Derived Suppressor Cells.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Chloroquine Downregulation of Intestinal Autophagy to Alleviate Biological Stress in Early-Weaned Piglets.Animals : an open access journal from MDPI · 2020Article
- Chloroquine Improves Deoxynivalenol-Induced Inflammatory Response and Intestinal Mucosal Damage in Piglets.Oxidative medicine and cellular longevity · 2020Article
- Does mammalian target of rapamycin or sestrin 1 protein signaling have a role in bone fracture healing?Turkish journal of medical sciences · 2019Article
- Inhibition of HIF-1α restrains fracture healing via regulation of autophagy in a rat model.Experimental and therapeutic medicine · 2019Article
- Effect of rapamycin on bone mass and strength in the α2(I)-G610C mouse model of osteogenesis imperfecta.Journal of cellular and molecular medicine · 2019Article
- Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles.Nature reviews. Drug discovery · 2017Review
- [Effect of calcitonin gene-related peptide on MC3T3-E1 osteoblast apoptosis and autophagy induced by serum starvation].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2017Article
- Chemical characterization of wound ointment (WO) and its effects on fracture repair: a rabbit model.Chinese medicine · 2017Article
- VGLL3 Regulates DAPK2-Mediated Autophagy During Osteoblast Differentiation.BioFactors (Oxford, England)Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy is a crucial mediating process for normal bone cell function and metabolism in physiology or pathology. Rapamycin has been demonstrated to induce the autophagy pathway by inhibiting the mammalian target of rapamycin (mTOR) pathway. However, the contribution of autophagy in orthopedic diseases is rarely reported. The aim of the present study was to evaluate the capacity of pharmacologically induced autophagy to modify disease function in a rat model of bone fracture. A femur fracture model was established via surgery in adult male Sprague-Dawley rats. Rapamycin (n=63 rats) or dimethyl sulfoxide (DMSO) vehicle control (n=63 rats) was administered intraperitoneally for 2, 4 and 6 weeks, and 21 randomly selected rats were sacrificed in each group at each time point. X-ray micro-computed tomography and hematoxylin and eosin staining were used to evaluate the extent of fracture healing in each group. The effects of rapamycin on autophagy, mTOR signaling and the expression levels of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) were analyzed using immunohistochemistry, immunofluorescence staining and western blot analysis. Rapamycin affected the mTOR signaling pathway in rats following fracture, as indicated by the inhibition of the phosphorylation of ribosomal protein S6, a target of mTOR, and activation of microtubule-associated protein 2 light chain 3, a key marker of autophagy. Histomorphometry and image examination indicated that the number of osteoblasts in each section was significantly (P<0.01) increased in the rapamycin group compared with the control group, and this was associated with a significant (P<0.05) increase in mineralized callus fraction. Furthermore, rapamycin treatment increased the expression levels of VEGF and PCNA in the rat callus tissue. These results suggest that rapamycin may serve a beneficial function in fracture healing, and that the underlying mechanism may involve the activation of autophagy.
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