Polypeptide for treating osteoporosis, preparation method and applications thereof

A technology of osteoporosis and polypeptide, applied in the field of bioengineering, to achieve good bone targeting effect

Inactive Publication Date: 2019-01-01
SHANGHAI CHANGZHENG HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, it is entirely possible that the kiss1 / Gpr54 receptor regulates bone remodeling, thereby affecting diseases such as osteoporosis
However, so far there is no relevant literature report

Method used

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  • Polypeptide for treating osteoporosis, preparation method and applications thereof
  • Polypeptide for treating osteoporosis, preparation method and applications thereof
  • Polypeptide for treating osteoporosis, preparation method and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] This example clarifies the expression of kiss1 and Gpr54 in osteoclast differentiation.

[0054] Principle: Bone marrow monocytes can differentiate into osteoclasts in one week under the continuous stimulation of cytokines M-CSF and RANKL. The genes involved in the regulation of osteoclasts should be highly expressed during the process of osteoclast differentiation. Therefore, we first detected the expression of Kiss1 and Gpr54 during osteoclast differentiation.

[0055] Methods: In this example, RANKL was used to induce the differentiation of mouse primary bone marrow mononuclear cells BMMs into osteoclasts, and the cellular RNAs of different induction days were collected, and then the expression levels of Kiss1 and Gpr54 mRNAs were detected during the osteoclast differentiation process.

[0056] Results and evaluation:

[0057] The result is as figure 1 As shown, the results show that Kiss1 and Gpr54 are up-regulated during osteoclast differentiation. This suggests...

Embodiment 2

[0059] This example confirms the role of kiss1 and its receptor Gpr54 in positively regulating bone mass, and concludes that knockout of Gpr54 or Kiss1 gene leads to osteoporosis.

[0060] Principle: The mouse kiss1 and its receptor Gpr54 gene are edited on the genome to lose their function, and kiss1 and Gpr54 knockout mice are obtained respectively. Bone parameter changes were analyzed by micro-CT 3D imaging technology.

[0061] Methods: The femurs of 8-week wild-type (WT) and Gpr54 knockout (KO) mice were removed, fixed in 4% paraformaldehyde for 24 hours, detected by micro-CT, and analyzed by 100 3D images under the growth plate.

[0062] RESULTS AND EVALUATION: The micro-CT scan imaging results showed that the Gpr54 knockout mice had significantly decreased bone mass, trabecular bone loss, and osteoporosis symptoms. The result is as figure 2 As shown, statistical results showed that compared with WT mice, Gpr54 knockout mice decreased nearly 50% in bone mineral density...

Embodiment 3

[0064] This example confirms that kiss1 and its receptor Gpr54 positively regulate osteoclast differentiation (in vivo / in vitro), and concludes that knockout of Gpr54 or Kiss1 leads to osteoclast activation (in vivo), and knockout of Gpr54 or Kiss1 leads to osteoclasts activation (in vitro).

[0065] Principle: Bone marrow mononuclear cells will differentiate into osteoclast precursor cells under the stimulation of cytokine M-CSF. At the same time, under the continuous stimulation of cytokine M-CSF and RANKL, the intercellular Contact with each other to fuse to form multinucleated cells, and then continue to differentiate to form mature osteoclasts with a sealing ring structure, expressing specific tartrate-resistant acid phosphatase (TRAP) to participate in the degradation of bone mineralization. Mature osteoclasts can adhere to the bone matrix and degrade bone by secreting protease, resulting in osteoporosis.

[0066] method:

[0067] In vivo osteoclast activity detection:...

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Abstract

The invention discloses a polypeptide for treating osteoporosis, wherein the amino acid sequence is (Asp-Ser-Ser)6-(D-Tyr)-Asn-(D-Trp)-Asn-Ser-Phe-(azaGly)-Leu-Arg(Me)-Phe-NH2((AspSerSer)6-Kp-10, SEQID NO:1). The present invention further discloses a preparation method of the polypeptide, wherein the preparation method comprises: polypeptide synthesis, polypeptide cleavage, and separation and purification of the crude polypeptide. The invention further relates to applications of the polypeptide in preparation of drugs for treatment of osteoporosis. According to the present invention, the research results prove that the knockout of the Gpr54 or Kiss1 gene can cause osteoporosis and excessive activation of osteoclasts, Kp-10 inhibits osteoclast differentiation, actin-ring formation and boneresorption by activating Gpr54, and (AspSerSer)6-Kp-10 has good bone targeting effect and cab effectively treat ovariectomy induced osteoporosis in vivo compared to Kp-10, such that the theoretical basis is provided for the treatment of osteoclast-related diseases.

Description

technical field [0001] The invention belongs to the field of bioengineering, and relates to a polypeptide for treating osteoporosis and its application. Background technique [0002] Osteoporosis is the most common bone-related disease and one of the diseases with the highest incidence. According to statistics, the incidence of osteoporosis in women after the age of 50 is about 50%, and the incidence in men is as high as 20%, and with the increase of age, the incidence rate also increases. With the aging of the population, the number of osteoporosis patients in my country has ranked first in the world. In the past 30 years, the number of osteoporosis patients in our country has increased by 300%. The latest statistics show that there are 90 million osteoporosis patients in my country, which has become a serious social problem. Excessive activation of osteoclasts is the main cause of osteoporosis. After menopause in women, due to a large decrease in estrogen, osteoclasts a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/00C07K1/06C07K1/34A61K38/16A61P19/10
CPCA61K38/00C07K14/00
Inventor 肖建如刘明耀罗剑李珍惜龚海熠程义云章涵堃
Owner SHANGHAI CHANGZHENG HOSPITAL
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