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Application of TGF-beta 1 inhibitor in preparation of drugs to treat diabetic bone healing disorder

A technology of TGF- and inhibitors, applied in the field of biomedicine, can solve problems such as lack of therapeutic drugs and measures, delay in jaw bone regeneration and repair, etc.

Inactive Publication Date: 2019-09-06
AFFILIATED STOMATOLOGICAL HOSPITAL OF NANJING MEDICAL UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] Diabetes mellitus (DM) has become the third major disease that threatens human health after tumors and cardiovascular diseases. Such patients often have problems such as tooth extraction trauma, fracture healing, and implant osseointegration delays in jaw bone regeneration and repair. However, Currently, there are no corresponding therapeutic drugs and measures in clinical

Method used

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  • Application of TGF-beta 1 inhibitor in preparation of drugs to treat diabetic bone healing disorder
  • Application of TGF-beta 1 inhibitor in preparation of drugs to treat diabetic bone healing disorder
  • Application of TGF-beta 1 inhibitor in preparation of drugs to treat diabetic bone healing disorder

Examples

Experimental program
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Effect test

Embodiment 1

[0027] Example 1 High expression of TGF-β receptor II (TβRII) on the surface of healthy human-derived bone marrow mesenchymal cells (H-BMSCs) and diabetic patient-derived bone marrow mesenchymal cells (DM-BMSCs) under high-glucose and high-insulin culture environment.

[0028] In vitro isolation and culture of human-derived bone marrow mesenchymal cells: clinically healthy people (no history of diabetes, fasting blood glucose FBG6.0mmol / L; glycosylated blood glucose protein> 6.5%; fasting insulin > 10mIU / L, or fasting blood glucose (mmol / L) × fasting insulin (mIU / L) > 60), alveolar bone debris was obtained from the reamer drill during dental implant surgery. Transfer the petri dish containing the alveolar bone fragments to a microbial safety kitchen, and operate as follows: spread the bone fragments evenly on the petri dish, and place it upside down in the incubator for 30 minutes. Add 5ml of low-glucose medium or 5ml of high-glucose medium to healthy human bone tissue and bon...

Embodiment 2

[0055] Example 2 High expression of TGF-β1 in healthy human-derived bone marrow mesenchymal cells (H-BMSCs) under high-glucose and high-insulin culture environment.

[0056] The in vitro isolation and culture of healthy human-derived bone marrow mesenchymal cells (H-BMSCs) is the same as in Example 1, and H-BMSCs are cultured in low-sugar and high-sugar medium, adding or not adding insulin (200 μIU / ml) simultaneously, for 1 week Afterwards, total cell protein was extracted, and western blot detection method analyzed TGF-β1 expression situation (method is the same as embodiment 1, wherein, TGF-β1 (1:1000 skim milk dilution), β-actin (1:1000 skim milk dilution)) , the result is as figure 2 shown by figure 2 It can be seen that the high-glucose and high-insulin culture environment can promote the expression of TGF-β1 in H-BMSCs.

Embodiment 3

[0057] Example 3 TGF-β1 signaling pathway is highly expressed in bone marrow mesenchymal cells (DM-BMSCs) derived from diabetic patients.

[0058] The in vitro isolation and culture of diabetic patient-derived bone marrow mesenchymal cells (DM-BMSCs) is the same as in Example 1. Extract DM-BMSCs cell total protein, western blot detection method analyzes TGF-β1 signaling pathway expression situation (method is the same as embodiment 1, wherein, TGF-β1 (1:1000 skimmed milk dilution), P-Smad3 (1:1000 skimmed milk diluted), Smad3 (1:1000 skimmed milk diluted), β-actin (1:1000 skimmed milk diluted)), the results are as follows image 3 as shown, image 3 Among them, H-BMSCs(NG) represent bone marrow mesenchymal cells cultured in low sugar from healthy people, as a control. Depend on image 3 It can be seen that the TGF-β signaling pathway is highly expressed in DM-BMSCs cells, and the expression of TGF-β1 and P-smad3 is enhanced.

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Abstract

The invention discloses application of a TGF-beta 1 inhibitor in the preparation of drugs to treat diabetic bone healing disorder and belongs to the technical field of biopharmacy. A series of studiesby the inventor verifies that the TGF-beta 1 inhibitor can promote autophagy of diabetic bone marrow mesenchymal cells so as to inhibit cell senescence, thereby giving rise to the ability to promoteosteogenic differentiation. Therefore, the TGF-beta 1 inhibitor is applicable to the preparation of drugs to promote the osteogenic differentiation of diabetic bone marrow mesenchymal cells or drugs to promote diabetic bone healing. The problem is solved effectively herein that drugs to treat diabetic bone healing are absent in the prior art.

Description

technical field [0001] The invention relates to the application of TGF-β1 inhibitors in the preparation of medicines for treating diabetic bone healing disorders, and belongs to the technical field of biomedicine. Background technique [0002] Diabetes mellitus (DM) has become the third major disease that threatens human health after tumors and cardiovascular diseases. Such patients often have problems such as tooth extraction trauma, fracture healing and implant osseointegration delays in jaw bone regeneration and repair. However, At present, there are no corresponding therapeutic drugs and measures clinically. [0003] Transforming growth factor (TGF-β1), as a member of the TGF-β superfamily, participates in the TGF-β signaling pathway to regulate cell life activities such as growth, differentiation, and apoptosis. [0004] There is a large amount of TGF-β1 (200ug / kg) in the bone matrix. When the bone tissue is damaged or rebuilt, osteoclasts destroy the bone matrix, so t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4439A61K9/08A61P3/10A61P19/08
CPCA61K9/08A61K31/4439A61P3/10A61P19/08
Inventor 张平江宏兵傅瑜徐荣耀郭松松程杰袁华杜一飞李盛
Owner AFFILIATED STOMATOLOGICAL HOSPITAL OF NANJING MEDICAL UNIV
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