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Application of CXCL12/CXCR4 signaling pathway as target spot in preparation of medicine for treating or preventing heterotopic ossification

A heterotopic and drug-based technology, applied in the field of biomedicine, can solve unclear problems

Pending Publication Date: 2022-03-01
THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The mechanisms responsible for the formation of new bone in ectopic entheses remain unclear

Method used

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  • Application of CXCL12/CXCR4 signaling pathway as target spot in preparation of medicine for treating or preventing heterotopic ossification
  • Application of CXCL12/CXCR4 signaling pathway as target spot in preparation of medicine for treating or preventing heterotopic ossification
  • Application of CXCL12/CXCR4 signaling pathway as target spot in preparation of medicine for treating or preventing heterotopic ossification

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Embodiment 1 Model establishment and general experimental method

[0052] All animal experiments were approved by the Ethics Committee of the applicant's unit and carried out in strict accordance with the requirements.

[0053] 1. Establishment of spontaneous arthritis DBA / 1 mouse model

[0054] Male 8-week-old DBA / 1 mice (Beijing Weitong Lihua Experimental Animal Company) were obtained, and 9 mice / cage were raised together. They were divided into experimental group and control group, with 3 cages in each group.

[0055] Inflammation score was recorded to observe the clinical symptoms of arthritis, mice were scored twice a week, 0: no symptoms; 1: redness and swelling of one toe; 2: redness and swelling of more than one toe; 3: toe deformity; 4 : Foot deformity or ankle joint involvement. Both hind paws were evaluated to obtain a maximum score of 8, divided by the foot number 2, and the average value recorded.

[0056] The osteogenic sites were scanned by μCT at 8, ...

Embodiment 2

[0073] Example 2 High expression of CXCL12 at the site of ectopic new bone formation in the DBA / 1 mouse model

[0074]As shown in Figure 3, CXCL12 in ectopic osteogenesis sites was high in AS-related animal models (including DBA1 spontaneous inflammatory osteogenesis model, (proteoglycan-induced spondylitis) PGIS model and (semi-Achilles tendon transection) SMTS mouse model) Express.

[0075] In the AS-related animal model DBA1 spontaneous inflammatory osteogenesis model, the expression of CXCL12 in the plantar ectopic ossification site was significantly increased when the model was established to 20 weeks; in the PGIS model, when the model was established to 20 weeks, the paradiscal ligament of the spine was ectopic The expression of CXCL12 in the osteogenic site was significantly increased; in SMTS mice, the expression of CXCL12 in the ectopic osteogenic site at the start and end of the Achilles tendon was high when the model was established to 12 weeks.

Embodiment 3

[0077] Such as Figure 4 As shown, Micro-CT showed that in the DBA / 1 mouse inflammatory osteogenesis model (modeling 20 weeks), plerixafor significantly reduced the ectopic bone formation in the plantar of DBA1 mice, while the ectopic osteogenesis In the tissues, the Prx1+ osteogenic precursor cells in the plerixafor group were significantly reduced. Micro-CT showed that plerixafor significantly reduced ectopic bone formation at the paradiscal ligament of the spine in a mouse model of PGIS. SOFG staining showed that in the mouse spinal paradiscal ligament osteogenesis model, plerixafor significantly reduced the ectopic bone formation in the spinal paradiscal ligament. In the ectopic osteogenic tissue, the Sca1+ osteogenic precursor cells in the plerixafor group were significantly reduced. Micro-CT showed that in a mouse model of SMTS, plerixafor significantly reduced ectopic bone formation in the Achilles tendon of Achilles tendon hemisection mice. SOFG staining showed that...

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Abstract

The invention belongs to the field of biological medicine, and relates to application of a CXCL12 / CXCR4 signal channel in preparation of a medicine for treating or preventing heterotopic ossification. According to the application disclosed by the invention, high expression of the ectopic new bone formation part CXCL12 in an ankylosing spondylitis (AS) patient and an AS related animal model is found for the first time, and after CXCR4 is inhibited by adopting plerixafor, ectopic osteogenesis of a mouse is obviously reduced. The invention also provides an application of the CXCL12 detection reagent in preparation of a heterotopic ossification detection reagent or kit, and an application of the CXCL12 / CXCR4 signal channel inhibitor in preparation of drugs for treating or preventing heterotopic ossification. Taking ankylosing spondylitis heterotopic ossification as an example, plerixafor has a good inhibition effect.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to the application of CXCL12 / CXCR4 signaling pathway as a target in the preparation of drugs for treating or preventing heterotopic ossification. Background technique [0002] Heterotopic ossification (HO) is characterized by pathological heterotopic bone formation in soft tissues such as muscles, tendons, and ligaments adjacent to bone tissue and joints. Heterotopic ossification is most commonly associated with trauma such as spinal cord injury, brain injury, head injury, burns, fractures, muscle contusions, combat-related trauma, and surgery (especially arthroplasty). In addition, HO may occur in patients undergoing neuromuscular blockade to manage adult respiratory distress syndrome and in patients with nontraumatic myelopathy. In rare cases, HO may manifest as part of a genetic disorder and is sometimes associated with lower motor neuron disorders. Consequences of HO can include, inter...

Claims

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Application Information

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IPC IPC(8): G01N33/68C12Q1/6883A61K45/00A61K31/395A61P19/08
CPCG01N33/6893C12Q1/6883A61K45/00A61K31/395A61P19/08G01N2333/521G01N2800/10C12Q2600/158
Inventor 刘辉崔昊文李翔李梓濠陈斯文代国王海涛巴布尔·海里力
Owner THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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