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Diagnostic marker of bone destructive disease and application of diagnostic marker

A destructive, disease-based technology that can be used in disease diagnosis, biological testing, biomaterial analysis, etc., to solve problems that affect the quality of life of patients

Active Publication Date: 2019-10-15
INST OF CHINESE MATERIA MEDICA CHINA ACAD OF CHINESE MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The above-mentioned bone destructive diseases are accompanied by serious complications such as pain, joint and bone deformities, which seriously affect the quality of life of patients

Method used

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  • Diagnostic marker of bone destructive disease and application of diagnostic marker
  • Diagnostic marker of bone destructive disease and application of diagnostic marker
  • Diagnostic marker of bone destructive disease and application of diagnostic marker

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Example 1 Changes in the expression of RNase L in the course of CIA rats

[0057] A total of 32 male SD rats with a body weight ranging from 160 to 180 g were selected, randomly divided into a blank control group (12 rats) and a model group (20 rats), and adaptively fed for 1 week. A collagen-induced arthritis (CIA) model was established one week later, and samples were collected on days 7, 14, 21, and 28 after the second immunization. Each sample included rats in the blank control group and the model group. All animals were fed a standardized diet and were not restricted in their activities.

[0058] 1. Effects on the clinical manifestations of CIA rats

[0059] On the 3rd day after the second immunization, the rats in the model group appeared symptoms of redness and swelling in the hindlimbs, which gradually involved the forelimbs. As time went by, the swelling of the knee joints of the hindlimbs gradually increased, and the degree of redness and swelling of the ankl...

Embodiment 2

[0064] Example 2 Effect of RNase L on the pathogenesis and bone destruction of CIA mice

[0065] Wild-type (WT) C57BL / 6 mice and RNase L gene knockout (RNase L - / - ) mice were randomly divided into 4 groups, namely WT-control (Control) group, WT-model (Model) group, RNase L - / - -Control group, RNase L - / - -Model group. In the Model group, the collagen-induced arthritis (CIA) model was established.

[0066] 1. Symptoms such as joint swelling and deformity

[0067] By establishing a CIA rat model, it was found that the expression of RNase L gradually increased over time. What is the effect of RNaseL on bone destruction in RA? The relationship between RNase L and RA was further clarified by establishing the CIA model of RNase L gene knockout mice. Redness and swelling of multiple interphalangeal joints appeared, and gradually spread to the foot pads and ankle joints, sometimes involving the forelimbs, and the degree of joint redness and swelling gradually decreased over time...

Embodiment 3

[0075] Example 3 Effect of RNase L on the pathogenesis and bone destruction of CAIA mice

[0076] CIA is an internationally recognized animal model of rheumatoid arthritis. In addition, we also adopted a collagen-antibody induced arthritis (CAIA) model, which is more clinical in its onset. C57BL / 6 WT mice and RNase L knockout mice were randomly divided into 4 groups, namely WT-Control group, WT-Model group, RNase L - / - -Control group, RNase L - / - -Model group. In the Model group, the type II collagen antibody-induced arthritis (CAIA) model was established.

[0077] 1. Effects on clinical manifestations of CAIA mice

[0078] On the 7th day after modeling, the mice in the model group began to have joint redness and swelling in the hind limbs, which gradually spread to the foot pads and ankle joints, and sometimes involved the forelimbs. In the later stage, the joint redness and swelling gradually reduced and symptoms of deformity and stiffness appeared. Under the same condit...

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Abstract

The present invention provides application of ribonuclease L, namely RNase L or a fragment thereof as a reactive antibody or ribonuclease L gene to preparation of a reagent for diagnosis of a bone destructive disease. It is found that RNase L promotes the differentiation, activation and bone resorption function of mouse BMMs to TRAP-positive osteoclasts, and increases the expression of osteoclastdifferentiation marker genes TRAP, MMP-9, CtsK and other mRNA; secondly, the protein expression of RNase L in a CIA rat model is increased with the progress of the disease; and finally, the degree ofbone destruction in CIA mice and CAIA mice of a rheumatoid arthritis model after RNase L gene knockout is significantly reduced. The present invention demonstrates that RNase L plays a key role in bone destruction and can serve as a marker for bone destructive diseases.

Description

technical field [0001] The invention belongs to the field of biological detection, and in particular relates to a diagnostic marker for bone destructive diseases and an application thereof. Background technique [0002] Ribonuclease has the function of specifically degrading RNA, and plays an irreplaceable role in regulating RNA metabolism, gene expression and protein synthesis. RNase L is one of the key enzymes for the effect of IFN on virus infection and cell proliferation in the 2-5A system. IFN induces the expression of the 2-5A synthetase gene family (OAS). 2-5A synthetase, upon activation by dsRNA, converts the ATP molecule into pyrophosphate (ppi) and a series of unique 5′-phosphorylated 2′-5′-linked oligoadenylates, termed 2-5A. 2-5A binds to RNase L and becomes a dimer, which leads to the degradation of single-stranded virus and cellular RNA, and inhibits the replication of certain viruses and cell proliferation. Although originally described as an antiviral drug...

Claims

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Application Information

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IPC IPC(8): G01N33/573G01N33/68G01N33/532G01N33/533
CPCG01N33/573G01N33/6893G01N33/532G01N33/533G01N2800/10G01N2800/105G01N2800/108
Inventor 孔祥英苏晓慧林娜吴宣苏红昌
Owner INST OF CHINESE MATERIA MEDICA CHINA ACAD OF CHINESE MEDICAL SCI
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