Medicine for treating bone metabolic diseases and application thereof

A metabolic disease and drug technology, applied in the field of biomedicine, can solve the problems such as Epiregulin, which has not been recorded, and achieve the effects of preventing and treating bone loss, promoting osteogenic differentiation, and inhibiting adipogenic differentiation

Pending Publication Date: 2021-11-05
天津医科大学朱宪彝纪念医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] At present, there is no record in the prior art that Epiregulin has the function of regulating bone homeostasis and bone mass.

Method used

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  • Medicine for treating bone metabolic diseases and application thereof
  • Medicine for treating bone metabolic diseases and application thereof
  • Medicine for treating bone metabolic diseases and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0077]This example analyzes the effect of epiregulin overexpression lentivirus on the osteogenic differentiation of BMSCs.

[0078] Epiregulin overexpression lentivirus was used to infect BMSCs (Ereg OE LV group), and BMSCs infected with control virus was used as a control (Ctrl OE LV group). Total RNA was collected from the cells at 48 hours, and the overexpression efficiency was detected by qRT-PCR. At the 3rd day of osteogenesis induction, the cells were collected to extract total RNA, and the expression of osteogenesis-related gene mRNA was detected. The results were as follows: Figure 1A and Figure 1B As shown, in BMSCs infected with Epiregulin overexpressing lentivirus, Epiregulin gene (Ereg), Runt-related transcription factor 2 gene (Runx2), zinc finger structure transcription factor Osterix gene (Osx), alkaline phosphatase gene (ALP) The mRNA expression of osteopontin gene (Opn) was significantly up-regulated, which were 3.4, 2.5, 2.5, and 2.4 times that of the contr...

Embodiment 2

[0081] This example analyzes the effect of Epiregulin overexpression lentivirus on the adipogenic differentiation of BMSCs.

[0082] BMSCs were infected with Epiregulin overexpression lentivirus (Ereg OE LV group), and BMSCs infected with control virus were used as control (Ctrl OE LV group). When the cell density reached 100%, adipogenic induction was carried out, and the cells were collected for 48 hours to extract total RNA and detect The expression of key gene mRNA for adipogenesis, such as Figure 2A As shown, in BMSCs infected with Epiregulin overexpressing lentivirus, the mRNA expressions of adipogenic differentiation marker genes Pparγ, C / ebpα, Fabp4 and adipsin were all decreased by 73%, 71%, 76% and 68% respectively; Extract the total protein of cells, and detect the expression of proteins encoded by adipogenesis-related genes at the protein level, such as Figure 2B and Figure 2C As shown, in BMSCs infected with Epiregulin overexpressing lentivirus, the protein ...

Embodiment 3

[0085] This example analyzes the effect of Epiregulin recombinant protein on the osteogenic differentiation of BMSCs.

[0086] Different doses (5ng / mL, 10ng / mL and 20ng / mL) of Epiregulin recombinant protein (Prospec, Shanghai, China) were added to the BMSCs medium, treated with PBS solution (vehicle) as a control, followed by osteogenesis induction, induction At 3 days, the cells were collected to extract total RNA, and the expression of osteogenesis-related gene mRNA was detected. At 14 days after induction, ALP staining was performed, and the staining results showed ( Figure 3A ), compared with the control group, with the increase of Epiregulin concentration, ALP staining deepened sequentially, qRT-PCR detection results ( Figure 3B ) showed that the mRNA expressions of osteogenic differentiation marker genes Runx2, Osx, Alp, and Opn were significantly increased, indicating that Epiregulin recombinant protein can promote osteogenic differentiation of BMSCs after treatment w...

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Abstract

The invention relates to a medicine for treating bone metabolic diseases and application thereof. The medicine comprises an epithelial regulatory protein (Epiregulator). It is found for the first time that Epiguulin participates in the bone marrow stromal cell osteogenesis/adipogenesis differentiation process, by improving expression of autophagy related genes ULK-1, Beclin-1, Atg5 and Atg7 and activating an autophagy signal channel, expression of bone marrow stromal stem cell osteogenesis differentiation marker genes Runx2, Osterix, alkaline phosphatase and osteopontin can be improved, and the adipogenic differentiation marker gene peroxisome proliferator activated receptor gamma, CCAAT enhancer binding protein alpha, fatty acid binding protein 4 and adipsin expression can be inhibited, so that bone marrow stromal stem cell osteogenic differentiation is promoted, adipogenic differentiation is inhibited, and it is found for the first time that the Epiregulator protein can effectively prevent and treat bone loss of ovariectomized mice.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and relates to a medicine for treating bone metabolic diseases and an application thereof. Background technique [0002] Bone marrow stromal stem cells (Bone mesenchymal stem cells, BMSCs) are a type of cells with multilineage differentiation potential, which can differentiate into osteoblasts, adipocytes, chondrocytes, tenocytes, myoblasts and visceral mesoderm cells. Bone marrow stromal stem cells, as the common progenitor cells of osteoblasts and adipocytes, have a competitive relationship between adipogenic and osteogenic differentiation, and play a vital role in bone maintenance. And adipogenic differentiation imbalance is a common phenomenon in many human diseases, such as osteoporosis, osteoporosis is generally age-related, is a bone metabolic disease, characterized by low bone density, osteopenia, bone micro Structural deterioration, adipocyte infiltration, and increased bone fragili...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/18A61P19/10A61P19/08
CPCA61K38/1808A61P19/10A61P19/08
Inventor 王宝利吴晓文周杰朱恩东袁海瑞
Owner 天津医科大学朱宪彝纪念医院
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