Active polypeptide capable of promoting osteogenesis and inhibiting osteoclast and application of active polypeptide

Abstract

The invention discloses an active polypeptide capable of promoting osteogenesis and inhibiting osteoclast and application of the active polypeptide. N-terminal serine is phosphorylated on the basis ofPTH1-34, and three repeated sequences of glutamic acid or aspartic acid are introduced at a C terminal; the sequence of the polypeptide is shown in SEQ ID NO:1 or SEQ ID NO:2, and the polypeptide hasosteoinductive activity similar to BMP2 and an osteoclast inhibiting effect similar to parathyroid hormones (PTH). Random coils of the polypeptide can be avoided by bonding the C-terminal repeated sequences of the polypeptide to the surface of a calcium phosphate material or a material with a calcium phosphate coating, no addition of organic reagents is needed, and therefore the activity of the polypeptide is protected effectively; furthermore, slow controlled release can be achieved through cleavage of peptide bonds, and long-term intermittent injection of the PTH1-34 can be avoided, so thatthe injection pain of patients is reduced, and effects of osteoblast promotion and osteoporosis inhibition are achieved; a conventional viewpoint that the PTH1-34 cannot be administered locally is changed.

Description

technical field [0001] The invention relates to the field of bone biomaterials and tissue engineering, in particular to an active polypeptide capable of promoting osteogenesis and inhibiting osteoclastosis and its application. Background technique [0002] According to available data, about 200 million people in the world suffer from osteoporosis, and its incidence rate has risen to the seventh among chronic diseases. In my country, the number of osteoporosis patients over 60 years old has exceeded 80 million, and the incidence of osteoporotic fractures in the elderly has also reached 6.3%-24.4%. Osteoporotic fractures heal slowly, and the risk of complications during the healing process is high. At the same time, osteoporotic fractures have high disability and mortality rates, which seriously affect the quality of life of patients and increase the burden on the health system. The World Health Organization (WHO) has listed osteoporosis as one of the three major diseases aff...

AI Technical Summary

Problems solved by technology

Teriparatide is currently the only bone formation-promoting drug approved by the US FDA. It can not only increase bone mass, inhibit bone resorption and reverse osteoporosis, but also may promote fracture healing. It is considered to be effective in the treatment of severe osteoporosis." "Breakthrough" progress, but the problem is that it is expensive, can only be administered by injection, can cause hypercalcemia, and even the risk of osteosarcoma, and cannot be used for a long time (2 years)

[0005] The biological activity of recombinant human parathyroid hormone (rhPTH 1-34) teriparatide is not stable enough, the main reason is that the polypeptide sequence is long (34 amino acids) and has a certain degree of flexibility, which may Curl occurs, and the spatial structure is still not stable, so the dominant conformation for binding to the receptor is not prominent, which affects the selectivity and activity intensity of binding to the receptor

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