74 results about "Osteoclast" patented technology

The invention provides a composite hydrogel for infectious bone defect repair and a preparation method thereof, and belongs to the technical field of bone defect repair, the composite hydrogel comprises a three-dimensional porous network structure hydrogel and a bioactive unit, and the bioactive unit is loaded in the three-dimensional porous network structure hydrogel; the hydrogel with the three-dimensional porous network structure is prepared from photo-crosslinked methacrylated silk fibroin and nano-hydroxyapatite; the bioactive unit comprises a strontium metal organic framework loaded with curcumin. According to the invention, the photo-crosslinked methacrylated silk fibroin provides excellent biocompatibility; as an ion / drug dual carrier, the strontium metal organic framework can continuously release strontium ions and bidirectionally regulate bone metabolism (promoting osteogenesis and inhibiting osteoclast), and the porous structure of the strontium metal organic framework can efficiently load a hydrophobic drug curcumin (Cur). Curcumin has strong antibacterial and anti-inflammatory functions; the nano-hydroxyapatite can obviously enhance the mechanical strength of the hydrogel.

The application discloses a flavonoid compound in eaglewood as well as a preparation method and application of the flavonoid compound, and relates to the technical field of medicines. The application extracts and separates a new compound from natural eaglewood, and the new compound is used in the preparation of anti-osteoporosis drugs. The compound is detected in vitro to obtain an induction effect of the compound on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts, so as to affect the formation of osteoclasts. Meanwhile, the compound can promote the bone development of zebra fish through RT-qPCR detection, which indicates that the compound has anti-osteoporosis activity. The separation method of the compound is simple and easy to operate.

The invention relates to the technical field of gene therapy and drug development, and provides application of a UCH37 inhibitor in preparation of a drug for treating osteoporosis. The expression level of UCH37 in blood of osteoporosis patients is obviously higher than that of UCH37 in blood of healthy people, and the UCH37 is in positive correlation with osteoclast active markers such as NFATC1 and MMP9. The UCH37 inhibitor is applied to preparation of the medicine for treating osteoporosis and directly targets UCH37, the curative effect does not depend on the expression change of ADRM1, no matter the ADRM1 of osteoporosis patients is in a low or high expression state, an osteoclast activation pathway can be stably blocked, the consistency of treatment effects of different individuals is ensured, the range of applicable people of the medicine is expanded, and the application prospect is broad. The compound has the characteristics of clear action mechanism and wide application range, and provides important theoretical basis and conversion prospect for developing novel and efficient medicines for treating osteoporosis.

The invention discloses an application of polygonatum kingianum exosome in preparation of medicines for preventing and treating osteoporosis, the polygonatum kingianum exosome has good biocompatibility, can significantly inhibit osteoclast differentiation, promote osteocyte differentiation, effectively target bone tissues and significantly improve osteoporosis conditions, and has potential in preparation of medicines for preventing and treating osteoporosis. The polygonatum kingianum exosome is rich in source, has natural components with potential activity, is low in cost and is suitable for large-scale batch production.

The present invention relates to a composition comprising 4-hexylresorcinol (4-HR) as an active ingredient for prevention or treatment of a bone disease, and a formulation thereof. The composition comprising 4-hexylresorcinol (4-HR) as an active ingredient, or an ointment thereof was found to improve bone thickness, density, and strength and control bone remodeling by promoting the differentiation of osteoblasts and suppressing the proliferation and differentiation of osteoclasts in osteoporosis-induced animal models. Thus, the composition or ointment comprising 4-hexylresorcinol (4-HR) as an active ingredient can be provided as a therapeutic agent for bone diseases including bone fracture, osteoarthritis, rheumatoid arthritis, and osteoporosis.

The invention provides application of linariin-6-O-glucoside in preparation of a product for preventing and treating osteoporosis, and relates to the field of biological medicine. According to the invention, dyeing experiments of alkaline phosphatase, alizarin red and tartaric acid resistant acid phosphatase prove that the sesaminin-6-O-glucoside has affinity for FPPS receptors, has the capability of promoting bone marrow mesenchymal stem cells to form bone cells, is superior to that of bisphosphate, and can inhibit the generation of osteoclasts; microCT (micro computed tomography) detection results show that the sesaminin-6-O-glucoside has the effect of relieving the osteoporosis and can promote the formation of bone trabecula. According to the application disclosed by the invention, it is proved for the first time that the sesaminin-6-O-glucoside has the effect of resisting osteoclast formation, and meanwhile, the sesaminin-6-O-glucoside also has a better osteogenesis effect, so that a basis is provided for developing the sesaminin-6-O-glucoside as a potential medicine for treating osteoporosis.

The present invention provides methods of inhibiting osteoclastogenesis or inhibiting osteoclast activity using fused imidazole derivative compounds and pharmaceutical compositions. These methods may be used to treat various bone destructive disorders.

The present application relates to the pharmaceutical use of 4-[9-(6-aminopurine)]-2(S)-hydroxybutyric acid methyl ester, in particular to its use in the preparation of a medicament for preventing and / or treating diseases associated with abnormal osteoclast activity. It has been found that 4-[9-(6-aminopurine)]-2(S)-hydroxybutyric acid methyl ester has a significant inhibitory effect on osteoclast differentiation, and intra-articular injection of 4-[9-(6-aminopurine)]-2(S)-hydroxybutyric acid methyl ester has a therapeutic effect on MIA-induced osteoarthritis. Therefore, 4-[9-(6-aminopurine)]-2(S)-hydroxybutyric acid methyl ester has the prospect of being developed into a therapeutic drug for diseases associated with abnormal osteoclast activity.

The invention discloses an osteoclast culture method as well as a culture medium and application thereof, the culture method is based on primary monocyte extraction, inoculation is performed according to a specific density, then quantitative M-CSF is added, and culture is performed overnight; on the second day, when the cell confluence degree of the mononuclear bone marrow hematopoietic stem cells is 5-30%, supplementing quantitative RANKL into each hole, continuously culturing for 2-4 days, then changing the solution, and obtaining mature osteoclasts on the sixth-seventh day. According to the invention, the optimization relationship among the cell activity, the cell density and the culture medium in the primary culture process of the osteoclast is deeply studied, and from the perspective of cost reduction and efficiency improvement, the use cost of cell factors is remarkably reduced, the number of times of liquid change is reduced, and the traditional culture time of 10-12 days (calculated from cell extraction) is shortened to 6-7 days. The average diameter of the mature osteoclast cultured by the method is larger, the number of fused cell nucleuses is larger, the space proportion of the mature osteoclast is not less than 80%, and the cell quality is obviously higher than that in the prior art.

The invention provides an application of miR-337 in preparation of a medicine for treating osteoporosis, which is used for the medicine for treating osteoporosis, and relates to the technical field of biomedicine. The research of the inventor finds that miR-337 can activate p53 to promote apoptosis of osteoclasts, has a certain treatment effect on osteoporosis, and can be used for preparing the medicine for treating osteoporosis; the nano vesicles derived from human umbilical cord mesenchymal stem cells have certain anti-inflammatory activity and have a positive effect on treatment of osteoporosis. According to the application disclosed by the invention, miR-337 is further loaded on nano vesicles derived from human umbilical cord mesenchymal stem cells, and the research of the inventor finds that the medicine has a good treatment effect on osteoporosis, provides a new strategy for preventing postmenopausal osteoporosis, and has remarkable clinical transformation potential.

[Problem]The present invention demonstrates that, when added to the culture, DHMBA inhibits the proliferation of mouse inflammatory macrophage RAW264.7 cells, promotes their cell death, and reduces their cell number. It also demonstrates that DHMBA suppresses the increased production of inflammatory cytokines in RAW264.7 cells cultured with LPS, and in particular, DHMBA treatment suppresses osteoclast formation in RAW264.7 cells stimulated with LPS. Thus, the present invention provides a useful means of treating inflammatory diseases using DHMBA.[Solution]The present invention is characterized by having an anti-inflammatory effect by including 3,5-dihydroxy-4-methoxy benzyl alcohol (DHMBA) as an active ingredient.

The invention discloses application of guaiacol in treatment of rheumatoid arthritis, and particularly relates to application of guaiacol in preparation of drugs for treating rheumatoid arthritis. Cell experiments prove that guaiacol can effectively down-regulate expression of proinflammatory factors in macrophages and up-regulate expression of anti-inflammatory factors, and has remarkable anti-inflammatory activity; animal experiments show that the guaiacol effectively relieves rheumatoid arthritis model mouse diseases, and the specific manifestation is that the guaiacol obviously relieves the mouse claw swelling degree, reduces the arthritis disease score, obviously improves joint inflammatory cell infiltration, repairs cartilage injury, inhibits osteoclast generation and reduces the number of joint apoptotic cells; meanwhile, the level of proinflammatory factors in serum of mice can be effectively reduced, and the level of proinflammatory repair factors can be up-regulated. The invention proves that guaiacol has a definite curative effect on rheumatoid arthritis, good biological safety and no obvious side effect, provides a new effective active component for the treatment of rheumatoid arthritis, and has a good prospect of being developed into the medicine for treating rheumatoid arthritis.

The present application relates to a kind of RANKL / NLRP3 dual-target inhibitor and its preparation method and application, belong to the field of pharmaceutical chemistry and biomedical technology.The indole compound, its optical isomer, pharmaceutically acceptable salt and hydrate provided by the present application have RANKL and NLRP3 dual-target inhibition activity, can be inhibited by inhibiting RANKL-RANK interaction, and inhibit inflammasome NLRP3 activity, regulate RANKL activity in osteoclast precursor cell, inhibit the formation of osteoclast, thereby reduce bone resorption, and improve the inflammatory response caused by rheumatoid arthritis, is expected to play the prevention and treatment of bone metabolic disease.

To provide a novel Lactobacillus paracasei strain with bone regeneration effects, and pharmaceutical and food compositions containing the same. [Solution] The present invention relates to a novel Lactobacillus paracasei L-30 and its uses, and more particularly to Lactobacillus paracasei L-30 (KCTC16035BP) which has the ability to promote the differentiation or formation of osteoblasts, the ability to suppress the differentiation or formation of osteoclasts, and the ability to promote immune activity, and which can regenerate bone, and to a pharmaceutical composition for the treatment or prevention of bone diseases containing the same.

The present application relates to the technical field of medicine, and more particularly to the application of beta-hydroxybutyric acid in the preparation of a drug for preventing and / or treating osteoporosis, including postmenopausal osteoporosis due to estrogen deficiency and diabetic osteoporosis, wherein the concentration of the beta-hydroxybutyric acid is 150 mM, the application of beta-hydroxybutyric acid in the preparation of a drug for inhibiting the differentiation of osteoclasts or inhibiting the formation of osteoclasts, wherein the beta-hydroxybutyric acid inhibits the differentiation of osteoclast precursor cells into osteoclasts, and the concentration of the beta-hydroxybutyric acid is 10 mM; the present application proves that beta-hydroxybutyric acid improves the bone microstructure of OVX mice and db / db mice, inhibits the differentiation of osteoclasts, and reduces bone resorption, thereby providing a new target for the prevention and treatment of osteoporosis.

The present application belongs to the field of medicine, and particularly relates to a new target point NCSTN for regulating bone metabolism and application of an agonist of the target point in preparation of a medicine for preventing or treating osteoporosis. One object of the present application is to provide a new target point NCSTN for regulating bone metabolism and application of the target point in promoting osteogenic activity, inhibiting osteoclast activity and treating osteoporosis. The present application first discovers a mechanism of treating osteoporosis by using an agonist of NCSTN, and has the effect of inhibiting mature differentiation of osteoclasts and promoting bone formation function of osteoblasts. This is very different from the previously reported mechanism of single inhibition of bone resorption or single promotion of bone formation, and the treatment of osteoporosis by simultaneously acting on bone resorption and bone formation can greatly reduce adverse reactions of the body to the medicine.

This invention discloses an osteoporosis biomarker circRNA and its applications, belonging to the field of biotechnology. This invention demonstrates that circBBS9 and its human homologs are expressed at elevated levels in osteoporosis. Simultaneously, a siRNA capable of knocking down circBBS9 expression was designed. This invention demonstrates that miR-423-3p is a downstream target of circBBS9. circBBS9 expression rapidly increases during osteoclast multinucleation, and inhibiting circBBS9 does not affect the differentiation of osteoclast mononuclear precursors, but weakens osteoclast multinucleation levels and bone resorption capacity, increasing bone mineral density in osteoporotic mice. This proves that the siRNA prepared in this invention can be used as a drug for the prevention and treatment of osteoporosis.

A method for constructing a microfluidic bone organoid-on-chip can continuously observe the impacts of different external factors on a bone tissue structure based on the “ternary regulation theory” of bone angiogenesis-bone resorption-osteogenesis coupling. The method includes: (1) building a visual three-dimensional cell cultivation platform to continuously observe impacts of different external factors on a ternary regulation theory based on angiogenesis of osteoclast precursors, osteoblasts and osteoclasts, such that a user is allowed to directly observe interactions among various kinds of cells; (2) designing microfluidic channels in a chip to allow a reagent involved to present a concentration gradient distribution in the chip; and (3) adding three bioinks including osteoblasts, osteoclasts and vascular endothelial cells respectively, so as to reflect the three cell components individually, in pairs, and as a whole in the chip. An apparatus for constructing a microfluidic bone organoid-on-chip is further provided.

The invention discloses an RIP3-mediated osteoarthritis animal model as well as a construction method and application thereof. The construction method comprises the following steps: delivering an effective dose of a genetic tool (such as an adenovirus vector) capable of expressing RIP3 protein into a knee joint subchondral bone area of an experimental animal, and realizing continuous overexpression of RIP3 through regular operation, so as to induce pathological characteristics highly similar to human osteoarthritis. The model stably shows typical OA phenotypes such as limb pain sensitization, subchondral bone loss and bone microstructure degeneration, osteoclast number increase and overlying cartilage degeneration. The invention reveals that the natural process of occurrence and development of the osteoarthritis can be directly simulated through specific overexpression of the RIP3 in the subchondral bone for the first time, and a brand-new and valuable tool is provided for researching the pathogenesis of the osteoarthritis and screening and evaluating medicines and therapies for treating the osteoarthritis.

The invention discloses a drug for combined treatment of breast cancer bone metastasis, the drug comprises two active components, namely a first active component and a second active component, the first active component is Bufalin and its pharmaceutically acceptable salt, prodrug and derivative, and the second active component is RANKL targeted drug; bufalin and a derivative thereof are combined with an RANKL targeted drug for use, the Bufalin and the derivative thereof are synergistically complementary, and the Bufalin is used for regulating and controlling a tumor microenvironment, reducing secretion of high bone metastatic breast cancer cells HMGB1 and inhibiting differentiation of mononuclear / macrophages in bone marrow to osteoclasts, so that occurrence and development of breast cancer bone metastasis are inhibited; the RANKL targeted drug can specifically block an OPG / RANK / RANKL signal channel, inhibit osteoclast activation, reduce bone destruction and block vicious circle of bone metastasis; when the two active ingredients are combined for use, the effect of inhibiting breast cancer bone metastasis is obviously better than that of single use of any active ingredient, the occurrence of breast cancer bone metastasis can be effectively prevented and delayed, the progress of bone metastasis focus is controlled, and the occurrence risk of bone related events is reduced.

The present application relates to a marker IBSP of lung cancer bone metastasis and application thereof. Specifically, the present inventors found that IBSP is highly expressed in both plasma and bone metastasis foci of lung cancer patients, and positively correlates with bone metastasis, thus can be used as a biomarker for detecting and diagnosing bone metastasis. Further studies have proved that the differentiation of macrophages to osteoclasts induced by IBSP is a necessary and sufficient condition for promoting lung cancer bone metastasis, thus IBSP inhibitors can inhibit bone metastasis. In addition, the present inventors first found that IBSP can directly induce the positive differentiation of macrophages to osteoclasts by regulating the Rac1-NFAT signaling pathway, thus inhibiting Rac1 can block the lung cancer bone metastasis induced by IBSP. The present application provides an effective target for diagnosing and treating lung cancer bone metastasis, and provides a new method for the prevention, diagnosis and treatment of bone metastasis.

The invention discloses application of quercidic acid in preparation of a medicine or a medicine composition for preventing or treating diseases or symptoms related to excessive glucocorticoid. According to the application disclosed by the invention, the protective effect of the quercidic acid on the GIONFH is verified through a preclinical model, and evidence that the quercidic acid can be applied to prevention or treatment of the GIONFH is provided. Animal experiments prove that the quercidic acid can inhibit methylprednisolone-induced rat GIONFH, and the action mechanism is related to inhibition of osteoclasts. The medicine or the medicine composition described by the invention can obviously improve the formation of necrotic fossa in femoral head of GIONFH, bone loss of bone trabecula, CTSK positive cell expression, osteoclast formation, bone resorption protein expression and osteoclast overactivity at a lower dosage, and provides a potential prevention and treatment scheme for treatment of GIONFH.

The application discloses a preparation method and application of a Tau-derived minimum functional peptide targeting a CUL3-RhoA axis, and an amino acid sequence of the Tau-derived minimum functional peptide is shown as SEQ ID NO. 4: GNIHHKPGGGQVEVKSEKLD. The application of the Tau-derived minimum functional peptide targeting the CUL3-RhoA axis in the preparation of a drug for treating diseases related to over-activation of osteoclasts belongs to the technical field of biological medicines, and the drug plays a pharmacological effect by blocking RhoA ubiquitination through CUL3, activating a RhoA-ROCK-MLC2 tension axis, and destroying a closed loop of osteoclasts. The Tau-derived minimum functional peptide can avoid application defects of full-length proteins, has low toxicity, high selectivity and physiological friendliness.

The invention provides application of malavirol in preparation of a medicine for treating osteoporosis, a malavirol sustained-release system and application of the malavirol sustained-release system, and relates to the technical field of medicines. The research of the inventor finds that malaviif restores the damaged macrophage intercellular function caused by OVX, removes apoptotic cells and reduces the release of inflammatory factors by antagonizing a CCR5 receptor and inhibiting the activation of a downstream signal channel of the CCR5 receptor, so that the inflammatory microenvironment in a marrow cavity is relieved, the bone homeostasis is recovered, the overexpression of osteoclasts is inhibited, and the osteoclast effect is improved. The composition is used for treating osteoporosis. According to the malaviif sustained release system provided by the invention, a drug library can be formed through subcutaneous injection, continuous release of malaviif is realized, the clinical compliance problems that the half-life period of malaviif is short and frequent administration is needed are solved, and a preferable medication scheme is provided for chronic disease management.

This invention belongs to the field of biomedical technology, specifically disclosing the application of cimicifuga in the preparation of drugs for treating periodontitis. Specifically, it relates to the application of cimicifuga in the preparation of drugs for treating periodontitis; and the application of cimicifuga in the preparation of drugs for treating alveolar bone defects (periodontal bone defects) caused by periodontitis. It also relates to the application of cimicifuga in the preparation of products for inhibiting macrophage polarization towards M1 and / or promoting macrophage polarization towards M2 in a single macrophage system. In this disclosure, cimicifuga has no significant toxicity to macrophages and has high safety; it targets and regulates macrophage polarization, inhibiting periodontal inflammation at its source; it significantly reduces inflammatory infiltration and osteoclast formation in periodontal tissues, effectively alleviating alveolar bone defects; and it provides a novel targeted immunotherapy drug for periodontitis, expanding the clinical application of single traditional Chinese medicine monomers.

The invention relates to a method for three-dimensionally printing bone organs and application, belongs to the technical field of three-dimensional printing, and provides a material composition for three-dimensionally printing the bone organs, the material composition comprises bio-ink, osteoblasts and osteoclasts, and the number ratio of the osteoblasts to the osteoclasts is 1: (2-3.5). Meanwhile, the invention provides a method for carrying out three-dimensional printing on a bone organoid by utilizing the material composition and a method for preparing a bone aging organoid. The bone organoid provided by the invention provides an ideal experimental platform for pathogenesis research of degenerative bone diseases, can be used for bone tissue engineering research, can also provide an important experimental basis for drug screening, treatment strategy optimization and the like of degenerative diseases such as osteoarthritis and the like, and has remarkable scientific value and application potential.

The application provides a strontium-doped polypeptide hydrogel and a preparation method, a composite biological scaffold and an application, and belongs to the technical field of biomedical materials.The strontium-doped polypeptide hydrogel comprises a three-dimensional nanofiber network formed by self-assembly of polypeptide phosphonated derivatives, and the three-dimensional nanofiber network is loaded with strontium ions.The three-dimensional nanofiber network is formed by self-assembly of strontium ions and polypeptide phosphonated derivatives, a novel hydrogel with mechanical adaptability, controllable degradability and bidirectional regulation function of osteogenesis-osteoclast is obtained, local targeted delivery of strontium ions is realized, and the functional regeneration of osteoporotic bone defects is realized in cooperation with the bone adhesion properties of polypeptides.

This invention relates to the application of SRGN in the treatment and diagnosis of osteoporosis, belonging to the field of biomedical technology. This invention reveals for the first time the key role of SRGN in the pathogenesis of osteoporosis, suggesting its potential as a novel therapeutic or diagnostic target for osteoporosis. Furthermore, this invention designs a novel neutralizing antibody against SRGN, 12E2, which effectively blocks the interaction between SRGN and SIGLEC15, showing significant inhibitory effects on osteoclast formation in both in vivo and in vitro models. In animal experiments, SRGN neutralizing antibody 12E2 or... Srgn Knockout significantly improved bone mineral density in mice. This invention provides novel molecular targets and strategies for the treatment or diagnosis of osteoporosis, and has promising clinical application prospects.

According to the application of the acanthopanax trifoliatus polysaccharide in preparation of anti-osteoporosis products, the anti-osteoporosis products comprise products for inhibiting osteoclast differentiation; the anti-osteoporosis product comprises a product for inhibiting the activity of an osteoclast TRAP enzyme. According to the invention, the acanthopanax trifoliatus polysaccharide is researched, the extraction process of the acanthopanax trifoliatus polysaccharide is optimized, and particularly, the structure analysis is performed on uniform polysaccharide obtained after the acanthopanax trifoliatus polysaccharide is purified, so that the in-vitro anti-osteoporosis activity of the purified acanthopanax trifoliatus polysaccharide component is researched, and a theoretical basis is provided for further development and utilization of the acanthopanax trifoliatus polysaccharide.

The invention relates to the technical field of traditional Chinese medicines, and particularly provides a traditional Chinese medicine composition for treating osteoporosis and a preparation method and application thereof. The traditional Chinese medicine composition for treating osteoporosis is prepared from fructus lycii, fructus schizandrae, fructus rubi, semen cuscutae, semen plantaginis, fructus ligustri lucidi, semen allii tuberosi, radix angelicae sinensis, rhizoma chuanxiong, herba epimedii, radix dipsaci and radix morindae officinalis. The traditional Chinese medicine composition can be preferably decocted into a decoction, has an action mechanism verified by research in the aspect of treating osteoporosis, and inhibits the function of osteoclasts by inhibiting the expression of RXR alpha and RXR beta, thereby reducing the number of osteoclasts and achieving the effect of treating osteoporosis.