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05188nas a2201297Ia 4500 |
| 001 |
10.1111-nyas.14568 |
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220427c20219999CNT?? ? 0 0und d |
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|a 00778923 (ISSN)
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| 245 |
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|a Progranulin promotes bone fracture healing via TNFR pathways in mice with type 2 diabetes mellitus
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| 260 |
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|b Blackwell Publishing Inc.
|c 2021
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| 856 |
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|z View Fulltext in Publisher
|u https://doi.org/10.1111/nyas.14568
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|a Type 2 diabetes mellitus (T2DM) significantly increases bone fragility and fracture risk. Progranulin (PGRN) promotes bone fracture healing in both physiological and type 1 diabetic conditions. The present study aimed to investigate the role of PGRN in T2DM bone fracture healing. MKR mice (with an FVB/N genetic background) were used as the T2DM model. Drill-hole and Bonnarens and Einhorn models were used to investigate the role of PGRN in T2DM fracture healing in vivo. Primary bone marrow cells were isolated for molecular and signaling studies, and reverse transcription-polymerase chain reaction, immunohistochemical staining, and western blotting were performed to assess PGRN effects in vitro. PGRN mRNA and protein expression were upregulated in the T2DM model. Local administration of recombinant PGRN effectively promoted T2DM bone fracture healing in vivo. Additionally, PGRN could induce anabolic metabolism during endochondral ossification through the TNFR2–Akt and Erk1/2 pathways. Furthermore, PGRN showed anti-inflammatory activity in the T2DM bone regeneration process. These findings suggest that local administration of exogenous PGRN may be an alternative strategy to support bone regeneration in patients with T2DM. Additionally, PGRN might hold therapeutic potential for other TNFR-related metabolic disorders. © 2021 New York Academy of Sciences.
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|a acan protein
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|a anabolic agent
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|a Anabolic Agents
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|a animal
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|a animal cell
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|a animal experiment
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|a animal model
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|a animal tissue
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|a Animals
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|a antiinflammatory activity
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|a Article
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| 650 |
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|a bone development
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| 650 |
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|a bone marrow cell
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| 650 |
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|a bone regeneration
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| 650 |
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4 |
|a Bone Regeneration
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| 650 |
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|a callus
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| 650 |
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|a cell isolation
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| 650 |
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|a chondrogenesis
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| 650 |
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|a clinical assessment
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| 650 |
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|a col2a1 protein
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| 650 |
0 |
4 |
|a collagen sponge
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| 650 |
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|a collagen type 2
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| 650 |
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4 |
|a complementary DNA
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| 650 |
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4 |
|a controlled study
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| 650 |
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4 |
|a cyclooxygenase 2
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| 650 |
0 |
4 |
|a cytoplasm protein
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| 650 |
0 |
4 |
|a Diabetes Mellitus, Type 2
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| 650 |
0 |
4 |
|a drug effect
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| 650 |
0 |
4 |
|a drug effect
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| 650 |
0 |
4 |
|a drug mechanism
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| 650 |
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4 |
|a enchondral ossification
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| 650 |
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4 |
|a fracture
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| 650 |
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4 |
|a fracture healing
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| 650 |
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4 |
|a fracture healing
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| 650 |
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4 |
|a Fracture Healing
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| 650 |
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4 |
|a Fractures, Bone
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| 650 |
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4 |
|a glucose
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| 650 |
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4 |
|a glyceraldehyde 3 phosphate dehydrogenase
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| 650 |
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4 |
|a human
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|a Humans
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|a immunohistochemistry
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|a impaired fracture healing
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|a in vitro study
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|a in vivo study
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|a inducible nitric oxide synthase
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| 650 |
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4 |
|a interleukin 1beta
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| 650 |
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4 |
|a ketamine
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| 650 |
0 |
4 |
|a male
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| 650 |
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4 |
|a messenger RNA
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| 650 |
0 |
4 |
|a metabolism
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| 650 |
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4 |
|a Mice
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4 |
|a Mice, Transgenic
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0 |
4 |
|a mitogen activated protein kinase 1
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| 650 |
0 |
4 |
|a mitogen activated protein kinase 3
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| 650 |
0 |
4 |
|a mitogen activated protein kinase p38
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| 650 |
0 |
4 |
|a molecular biology
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| 650 |
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4 |
|a mouse
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| 650 |
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4 |
|a non insulin dependent diabetes mellitus
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| 650 |
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4 |
|a non insulin dependent diabetes mellitus
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| 650 |
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|a nonhuman
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| 650 |
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|a Osteogenesis
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| 650 |
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|a pathology
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| 650 |
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|a progranulin
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|a progranulin
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4 |
|a Progranulins
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|a protein expression
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| 650 |
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|a protein kinase B
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| 650 |
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|a real time polymerase chain reaction
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| 650 |
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|a Receptors, Tumor Necrosis Factor, Type II
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|a reverse transcription polymerase chain reaction
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|a RNA extraction
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| 650 |
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|a signal transduction
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| 650 |
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|a somatomedin C
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| 650 |
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|a staining
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| 650 |
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|a stress activated protein kinase
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| 650 |
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|a tissue section
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| 650 |
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|a Tnf protein, mouse
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| 650 |
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|a Tnfrsf1b protein, mouse
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| 650 |
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|a TNF-α
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| 650 |
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4 |
|a transcription factor RelA
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| 650 |
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4 |
|a transgenic mouse
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| 650 |
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|a tumor necrosis factor
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| 650 |
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4 |
|a tumor necrosis factor receptor
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| 650 |
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4 |
|a tumor necrosis factor receptor 2
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| 650 |
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4 |
|a tumor necrosis factor receptor 2
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| 650 |
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4 |
|a tumor necrosis factor receptors
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| 650 |
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4 |
|a Tumor Necrosis Factor-alpha
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| 650 |
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4 |
|a type 2 diabetes
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|a unclassified drug
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| 650 |
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|a upregulation
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| 650 |
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|a Western blotting
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|a xylazine
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| 700 |
1 |
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|a Ding, Y.
|e author
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1 |
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|a Einhorn, T.A.
|e author
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1 |
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|a Hettinghouse, A.
|e author
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| 700 |
1 |
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|a Li, G.
|e author
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| 700 |
1 |
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|a Li, X.
|e author
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| 700 |
1 |
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|a Liu, C.-J.
|e author
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| 700 |
1 |
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|a Wei, J.
|e author
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