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Application of bone cell Wnt activator in preparation of medicine for accelerating fracture healing and preventing and treating bone nonunion and non-movement or weightless bone loss

An osteocyte and activator technology, applied in drug combinations, bone diseases, pharmaceutical formulations, etc., can solve problems such as reducing bone resorption, and achieve the effects of preventing and treating weightless bone loss, improving transformation and output, important clinical significance and strategic value.

Pending Publication Date: 2020-09-08
CHONGQING MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are many drugs to reduce bone resorption clinically, but there are few reports that such drugs are suitable for protecting astronauts during spaceflight

Method used

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  • Application of bone cell Wnt activator in preparation of medicine for accelerating fracture healing and preventing and treating bone nonunion and non-movement or weightless bone loss
  • Application of bone cell Wnt activator in preparation of medicine for accelerating fracture healing and preventing and treating bone nonunion and non-movement or weightless bone loss
  • Application of bone cell Wnt activator in preparation of medicine for accelerating fracture healing and preventing and treating bone nonunion and non-movement or weightless bone loss

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] In this example, the model construction of experimental mice was carried out.

[0067] Construction of Dmp1-Cre;Catnb f / + mice.

[0068] Canonical Wnt signaling in osteocytes activates daβcat in mice Ot, is a genetically modified experimental mouse prepared by our laboratory, referring to the literature Tu, X., et al., Osteocytes mediate the anabolic actions of canonical Wnt / beta-catenin signaling in bone. Proc Natl Acad Sci U S A, 2015.112 (5 ): p. E478-86. The mouse has been established using Cre-loxP technology, and is produced by mating Catnblox(ex3)×DMP1-8kb-Cre. The Catnb gene encoding β-catenin protein is inserted into the loxp sequence at the third exon, which is cut out after being recognized by Cre recombinase. Because the 3rd exon encodes the continuous phosphorylation site sequence of β-catenin, after continuous phosphorylation, it is degraded and cleared by ubiquitination, and β-catenin without the 3rd exon will not be degraded and stabilized in the cyto...

Embodiment 2

[0073] (1) Construction of Dmp1-Cre; Catnb f / + mouse fracture model.

[0074] The fracture model was made by surgical method. Select 8-10 week old mice, 20 in each of the control group and the experimental group, and the mice are anesthetized by intraperitoneal injection of 5% chloral hydrate (0.4mg / g) at 0.08ml / 10g. Thirty minutes later, mice were operated on under continuous inhalation of buprenorphine (0.1 mg / kg). After skin preparation on the right leg of the mouse, sterilize with 70% alcohol, cut the skin parallel to the tibia, and then use a No. 11 scalpel blade to cut a 6mm incision perpendicular to the skin above the kneecap, and bluntly separate the muscle to expose the upper 1 of the tibia / 2, then make an incision perpendicular to the medial side of the patella to expose the tibial plateau, use a 0.4mm syringe needle to penetrate the bone marrow from the tibial plateau, and then use a 0.26mm needle-free pin to insert into the bone marrow cavity, and the other end t...

Embodiment 3

[0082] (1) Construct a mouse fracture model when bone resorption is inhibited in wild-type mice.

[0083] One week before the operation, 0.1 mg / kg zoledronic acid was injected intraperitoneally, and a fracture model was produced by conventional surgery. The middle part of the right tibia of the mouse was selected as the fracture point, and intramedullary fixation was performed. The specific method was as shown in Example 1. X-ray was taken every week to observe the fracture healing of the mice. (2) Construct the fracture model of wild-type mice under the condition of bone resorption inhibition and intermittent continuous injection of PTH.

[0084] Four weeks before the operation, a daily subcutaneous injection of 100ng / g PTH (bachem, product number 4011474.0005) and an intraperitoneal injection of 0.1mg / kg zoledronic acid (Novartis Pharmaceuticals) one week before the operation were performed, and the fracture model was produced by the operation method shown in Example 1. , s...

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Abstract

The invention discloses application of a bone cell Wnt activator in preparation of a medicine for accelerating fracture healing and preventing and treating bone nonunion and non-movement or weightlessbone loss, and relates to the two fields of fracture healing and weightless bone protection. According to the invention, bone cell Wnt signal activation is proposed for the first time, so that the healing speed of bone fracture can be greatly increased, weightless bone loss can be completely prevented, various complications caused by the bone cell Wnt signal activation are avoided, and better clinical achievement conversion and output are facilitated. Meanwhile, bone cell Wnt signals are activated, delayed fracture healing or non-fracture healing and even bone nonunion can be treated, and theinfluence of osteoclast activity is avoided. Experimental data and a research direction are provided for delayed fracture healing and bone nonunion in clinical treatment. The invention also puts forward for the first time that: the activation of the bone cell Wnt signal can completely prevent and treat weightless bone loss, is beneficial for astronauts to prevent and treat weightless bone loss, and has important clinical significance and strategic value.

Description

technical field [0001] The invention relates to two fields of fracture healing and weightless bone protection, in particular, application of bone cell Wnt activator in preparation of medicines for accelerating fracture healing, preventing nonunion and non-exercise or weightless bone loss. Background technique [0002] Wnt signal is the first of the five major developmental signals, and its spatiotemporal regulation of osteogenesis, chondrogenic and adipogenic differentiation, and osteoclast differentiation. Wnt signaling research is popular and has the most achievements. Wnt has canonical and non-canonical pathways, which control cell fate during embryonic and postnatal periods, including cell proliferation, differentiation, polarization and migration. β-catenin is a canonical Wnt signal transmitter. When Wnt binds to its receptor Frizzld and co-receptor low-density lipoprotein (Lrp) 5 / 6, it stabilizes in the cytoplasm and enters the nucleus. Cooperative transcription factor...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K38/29A61K31/675A61P19/08A61P19/10
CPCA61K45/00A61K38/29A61K31/675A61P19/08A61P19/10A61K2300/00
Inventor 涂小林许文娟张一宁塞玛刘忻钰
Owner CHONGQING MEDICAL UNIVERSITY
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