37 results about "Osteoclast cell differentiation" patented technology

The invention provides a polyketone compound and application thereof in preparation of an osteoclast differentiation inhibitor, and relates to the technical field of marine natural products. The compound is obtained by separation and purification from a fermentation culture of a marine fungus talaromyces sp. GMIMD 02524 (the preservation number is GDMCC No. 66968), the compound is named as talaromyces furanone A, and the structure of the compound is as shown in the formula (I) in the specification. The compound can effectively inhibit RANKL-induced osteoclast differentiation by inhibiting an NF-kappa B signal channel in vitro, and has no obvious cytotoxicity at an effective concentration. Therefore, the compound talaromyfuranone A can be used for developing medicines for preventing and treating osteoclast-related osteolytic diseases such as osteoporosis and the like, and has a good application prospect.

The invention discloses application of a compound with a benzo-aza structure in preparation of a medicine for inhibiting osteoclast formation, the structure of the compound is shown as a formula (1), and R substituent is one of H, OCH3, Br, F and i-Pr. Cell experiments prove that the compound with the benzo-aza structure has a remarkable inhibiting effect on RANKL-induced osteoclast differentiation and marker gene expression, can be used as a candidate medicine which is novel in structure and is used for inhibiting osteoclast formation, and is used for targeting osteoclast to treat osteoporosis related diseases.

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 belongs to the technical field of biological medicines, discloses application of an STK26 gene in preparation of medicines for treating or preventing osteoporosis, and particularly relates to application of STK26 protein or a coding gene thereof in preparation of medicines for treating osteoporosis. According to the present invention, osteoclast differentiation is inhibited by knocking out the STK26 gene so as to treat osteoporosis, osteoclast differentiation can be promoted by overexpressing the specific STK26 protein and the encoded gene thereof so as to aggravate osteoporosis, and osteoporosis can be alleviated by specifically knocking out the STK26 in an ovariectomized osteoporosis mouse model and an age-related osteoporosis mouse model; overexpression of the STK26 recombinant protein can aggravate osteoporosis, and the STK26 protein and the coding gene thereof can be used as targets of clinical drug treatment, and have good prospects in screening and preparation of drugs for treating osteoporosis.

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 invention discloses an application of a branched ketonic acid dehydrogenase kinase (BCKDK) inhibitor in preparation of a medicine for preventing and treating osteoporosis. The invention finds that BCKDK can inhibit osteoblast differentiation and reduce the expression of endogenous BCKDK in osteogenic precursor cells so as to promote osteoblast differentiation; a small molecule compound inhibitor BT2 (3, 6-dichloro-2-benzothiophene carboxylic acid) of BCKDK promotes osteoblast differentiation of ovariectomized mice, inhibits osteoclast differentiation, reduces ovariectomized mouse bone loss and increases bone mass. According to the invention, the BCKDK inhibitor is proposed for the first time to be capable of promoting osteoblast differentiation, inhibiting osteoclast differentiation and increasing body bone mass by reducing BCKDK expression or inhibiting BCKDK protein biological functions, and has the effect of preventing and treating osteoporosis.

This invention relates to the application of 5-(tetradecoxy)-2-furoic acid (TOFA) in the preparation of drugs that inhibit osteoclast differentiation and function. Using a RANKL-induced mouse bone marrow macrophage osteoclast differentiation model, experiments demonstrated that TOFA can effectively inhibit osteoclast differentiation and function by inhibiting ROS and downregulating the expression of key osteoclast differentiation and function proteins such as Nfatc1, Src, and Ctsk. Furthermore, TOFA at concentrations of 40 μM and below showed no significant cytotoxicity, proving that TOFA can serve as a candidate compound for developing drugs that inhibit osteoclast differentiation and function, and for treating diseases caused by excessive activation of osteoclasts, thus possessing significant clinical application value. Additionally, by constructing a mouse ovariectomized osteoporosis model, the preventive and therapeutic effects of TOFA on estrogen-deficiency-induced osteoporosis were demonstrated.

The invention discloses application of a migration body in preparation of a medicine for inhibiting osteoclast differentiation or promoting osteogenesis. By optimizing cell culture conditions, the secretion amount of the migration body is remarkably increased, large-scale preparation can be realized, and the production cost is greatly reduced. According to the invention, active components in the migration body are enriched through pressure stimulation, so that the migration body has a more excellent effect of promoting bone defect repair. In addition, by utilizing the larger size and stable membrane structure of the migration body, the in-vivo residence time is prolonged, and the long-acting repair of single-time administration is realized, so that the problems of long-acting property and clinical transformation are solved. The migration body disclosed by the invention has a wide application prospect in the field of bone defect repair.

The present invention relates to a pharmaceutical composition containing Cbfβ (Core-binding factor subunit beta) expressing vascular smooth muscle cells or a culture fluid thereof as an active ingredient for the prevention or treatment of age-related diseases. It has been found that inhibition of Cbfβ expression in vascular smooth muscle cells promotes vascular calcification and osteoclast differentiation and that the culture fluid of Cbfβ-expressing vascular smooth muscle cells inhibits osteoclast differentiation. Thus, the composition can be advantageously utilized as a pharmaceutical composition for the prevention, treatment, alleviation, or diagnosis of age-related diseases.

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 application discloses a furan coumarin compound and application thereof in preparation of a drug for treating osteoporosis, and belongs to the technical field of drug research and development. 50 The furan coumarin compound has an IC of 37.86 nM, has no obvious cytotoxicity and systemic toxicity, can inhibit a key path of RANKL-induced osteoclast differentiation, and can be used for preparing the drug for treating osteoporosis.

A Lactobacillus paracasei L-30 strain deposited under Accession Number KCTC16035BP has ability to promote osteoblast differentiation or formation, inhibiting osteoclast differentiation or formation, and enhancing immune activity, thereby enabling bone regeneration. A pharmaceutical composition including the Lactobacillus paracasei L-30 strain, a lysate thereof, a culture thereof, an extract thereof, and / or a fraction of the extract may be used for treating or preventing bone diseases.

This invention discloses the application of OXR1 as a target in the preparation of drugs for treating osteoclast-related bone diseases. This invention reveals for the first time the crucial role of OXR1 in osteoclast differentiation: OXR1 directly binds to the KEAP1 protein, promoting the interaction between KEAP1 and p62, thereby mediating mitophagy, clearing excess reactive oxygen species generated during osteoclast differentiation, and maintaining mitochondrial homeostasis. Inhibiting OXR1 expression or function can effectively block osteoclast differentiation and reduce bone loss. Based on this, this invention provides two intervention strategies targeting OXR1: one is gene therapy using adeno-associated viruses carrying shRNA targeting OXR1; the other is screening and validating the novel use of the FDA-approved drug velpatasvir as an OXR1 inhibitor. In vitro and in vivo experiments confirmed that both significantly inhibit osteoclast activity and improve the osteoporotic phenotype in ovariectomized mice.

The invention discloses application of aporphine alkaloid Tinopaine A in hemsleya amabilis ox gall in preparation of a medicine for treating bone destruction related diseases, and belongs to the technical field of biological medicine. Experiments prove that the Tinpaine A monomer has an inhibition effect on osteoclast differentiation formation in vivo and in vitro; by regulating and controlling key factors for osteoclast formation, the compound has an inhibiting effect on in-vitro osteoclast formation under the concentration of 1-10 mu M and on in-vivo osteoclast formation of mice under the dosage of 2-20 mg / kg, can effectively reduce the number of osteoclasts and protect bone trabecula structures, and has an excellent treatment effect on bone destruction related diseases. The invention relates to a medicine for inhibiting osteoclast differentiation in vivo and in vitro and treating diseases related to bone destruction, which takes Tinopaine A as an active ingredient and can relieve bone destruction by regulating and controlling bone metabolism balance so as to achieve the purpose of treating the diseases related to bone destruction.

The invention relates to an application of N-sulfinyl formylhydrazone derivatives in preparation of drugs for inhibiting osteoclast generation and bone resorption, the N-sulfinyl formylhydrazone derivatives HTM-13, HTM-17, HTM-18, HTM-25 and HTM-37 can directly and effectively inhibit bone marrow macrophages from differentiating to osteoclasts by inhibiting the expression of osteoclast differentiation marker genes, and can be used for preparing drugs for inhibiting osteoclast generation and bone resorption. The cell toxicity is not shown when the concentration is not higher than 5 mu M. The N-sulfinyl formylhydrazone derivative has the beneficial effects that the N-sulfinyl formylhydrazone derivative provided by the invention can be used as a candidate drug molecule of a novel osteoclast differentiation inhibitor, and is used for developing a novel anti-bone resorption drug and treating diseases caused by overexpression of osteoclasts. Therefore, the invention has important clinical significance and application prospect.

The invention discloses application of a diaryl-substituted alpha-carbonyl amide compound. The diaryl-substituted alpha-carbonyl amide compound can be used for preparing medicines for treating osteoporosis, tumor bone metastasis or inflammatory bone destruction. Cell experiments prove that the diaryl-substituted alpha-carbonyl amide compound Z1-Z4 provided by the invention has a remarkable inhibition effect on osteoclast differentiation and bone resorption induced by RANKL, has no obvious cytotoxicity, and can be used as a candidate drug with a novel structure for inhibiting osteoclast differentiation and bone resorption; the method is used for targeting osteoclast to treat bone mass loss related diseases.

This invention provides a concentration gradient cell culture system that solves the problem of large errors in manual drug addition and the difficulty in constructing a stable, continuous concentration gradient in studies on the control of osteoclast progenitor cell differentiation using propionic acid-GPR43. [Solution] The system comprises a housing assembly with an inner container, a first liquid storage cylinder 2, a second liquid storage cylinder 3, a tuned crossbeam 4, an adjustable screw rod 5, a flow-dividing branch pipe array frame, a spiral mixing unit, a porous diffusion plate, and a culture tray 9. The tuned crossbeam is driven by the adjustable screw rod to synchronously supply liquid from both liquid storage cylinders. After gradient distribution by the flow-dividing branch pipe array frame and mixing by the spiral mixing unit, the porous diffusion plate forms a continuous and stable propionic acid concentration gradient field on the culture tray. This avoids manual errors, provides accurate concentration gradients to RAW264.7 and BMMs cells in a single experiment, and supports the calculation of dose-effect curves and IC50, as well as the elucidation of the mechanism of osteoclast differentiation control by propionic acid-GPR43 signaling.

To provide a means for inhibiting osteoclast differentiation. [Solution] A composition for inhibiting alveolar bone resorption and / or osteoclast differentiation, which comprises glycyrrhetinic acid, and cetylpyridinium chloride and / or isopropylmethylphenol.

This invention discloses an injectable bone powder with anti-inflammatory biological activity, its preparation method, and its application. The bone powder is a hydrogel internally loaded with a hydroxyapatite composite material, wherein the hydroxyapatite composite material is hydroxyapatite with membrane vesicles coated on its surface; the membrane vesicles are derived from pulp-derived suppressor cells; the mass-to-volume ratio of the hydroxyapatite composite material to the hydrogel is 20-30%. This injectable bone powder with anti-inflammatory biological activity, containing membrane vesicles derived from pulp-derived suppressor cells coated on the surface of the hydroxyapatite, has biological effects that inhibit T cell proliferation and macrophage differentiation into osteoclasts, thus blocking the inflammatory environment, suppressing the inflammatory response, and promoting alveolar bone repair and regeneration.

The invention relates to an application of a (1-phenyl-1H-pyrazole-3, 4, 5-triyl) tri (phenyl ketone) derivative in preparation of a medicine for resisting bone resorption and inhibiting osteoclast differentiation, and the (1-phenyl-1H-pyrazole-3, 4, 5-triyl) tri (phenyl ketone) derivative X-1 and X-4 inhibit formation of TRAP + mononuclear osteoclast precursor cells, and the (1-phenyl-1H-pyrazole-3, 4, 5-triyl) tri (phenyl ketone) derivative X-1 and the (1-phenyl-1H-pyrazole-3, 4, 5-triyl) tri (phenyl ketone) derivative X-4 inhibit formation of TRAP + mononuclear osteoclast precursor cells. And the (1-phenyl-1H-pyrazole-3, 4, 5-triyl) tri (phenyl ketone) derivatives X-2, X-3 and X-5 selectively block the further differentiation of the TRAP + osteoclast precursor cells into the mature osteoclast. The (1-phenyl-1H-pyrazole-3, 4, 5-triyl) tri (phenyl ketone) derivative has the beneficial effects that the (1-phenyl-1H-pyrazole-3, 4, 5-triyl) tri (phenyl ketone) derivative provided by the invention can be used as a novel candidate drug molecule of an inhibitor for resisting bone resorption and osteoclast differentiation, and is used for developing a novel inhibitor for osteoclast differentiation.

The invention discloses an application of azadirachtin in preparation of a medicine for preventing and treating osteoporosis. In-vitro and in-vivo experiments of the system prove that Nim remarkably inhibits differentiation of mouse bone marrow-derived mononuclear / macrophages induced by M-CSF and RANKL to osteoclasts. The Nim can also specifically induce the formed mature osteoclast to generate apoptosis. In the in-vivo osteoporosis model, Micro-CT three-dimensional reconstruction, bone parameter analysis and Hamp are carried out; the consistency of E dyeing results shows that Nim intervention effectively reverses bone trabecular structure damage and bone mass loss caused by ovariectomy, and partially recovers a bone microstructure. The invention proves that Nim effectively controls pathological bone resorption through double mechanisms of inhibiting osteoclast differentiation and promoting mature osteoclast apoptosis, and obviously improves bone loss caused by osteoporosis. The compound is clear in action effect and concentration-dependent, shows specific regulation and control capability on osteoclasts under an effective dose, and provides an important experimental basis for developing efficient anti-osteoporosis medicines.

The invention provides application of an HIF-2alpha inhibitor in preparation of a medicine for treating hypoxia-related stomatitis bone loss diseases. Experiments provided by the invention show that HIF-2alpha activates the expression of a key gene Camk4 for promoting osteoclast differentiation under the hypoxia condition, and the osteoclast differentiation promoting effect of the Camk4 is exerted; and the HIF-2 alpha inhibitor can be used for remarkably inhibiting osteoclast differentiation. Therefore, the HIF-2 alpha inhibitor can be used for treating the hypoxia-related stomatitis bone loss disease, and is expected to remarkably improve the treatment effect of the stomatitis bone loss disease when being used as an oral cavity-related treatment or prevention medicine.

The application discloses application of a migration body in preparation of a medicine for inhibiting osteoclast differentiation or promoting osteogenesis. The application significantly improves the secretion amount of the migration body by optimizing cell culture conditions, realizes large-scale preparation, and greatly reduces production cost. The application also enriches active ingredients in the migration body by pressure stimulation, so that the migration body has more excellent effect of promoting bone defect repair. In addition, the migration body has larger size and a stable film structure, prolongs in-vivo retention time, realizes long-acting repair by single administration, and further solves the long-acting and clinical transformation problems. The migration body has wide application prospect in the field of bone defect repair.

The application provides a preparation method and application of a biofunctionalized polyether ether ketone implant, wherein polyether ether ketone is subjected to surface modification through strong acid treatment, and is combined with strontium-doped bioactive glass by using a sol-gel method, so as to endow the polyether ether ketone with the ability of promoting osteogenic differentiation of bone marrow mesenchymal stem cells and inhibiting osteoclastic differentiation of mononuclear macrophages. Performance test results show that the contact angle of the acidized and surface-modified PEEK is reduced to different levels, which indicates that the hydrophilicity of the PEEK is significantly improved. At the same time, the proliferation and growth activity of bone marrow mesenchymal stem cells on the surface of the Sr-SPK are also better than before the surface modification. Differentiation test results show that, compared with the PEEK, the Sr-SPK can obviously promote the osteogenic differentiation of rat bone marrow mesenchymal stem cells, can obviously inhibit the differentiation of rat mononuclear macrophages into osteoclasts, and can obviously inhibit the formation of osteoclasts, and the biofunctionality is better.

The application provides a kind of polyarylether sulfone ketone surface biomimetic mineralization hydrogel coating, its preparation method and application in bone repair.The biomimetic mineralization hydrogel coating is obtained by simulating body fluid mineralization of hydrogel coating, and apatite layer is formed in the interior and surface of hydrogel coating, the hydrogel coating includes polymer network and calcium phosphate oligomer uniformly dispersed therein, which is anchored to the surface of polyarylether sulfone ketone base.The introduction of calcium phosphate oligomer effectively solves the problem of inorganic phase agglomeration and improves the uniformity of mineralization.The mineralized hydrogel coating can significantly promote the expression of osteoblast MC3T3-E1 osteogenic activity and inhibit the differentiation of RAW264.7 cells into osteoclasts.The biomimetic mineralization hydrogel coating described in the application has dual biological activity of promoting bone formation and inhibiting bone resorption, and is suitable for surface modification of polyarylether ketone bone implants, and has wide application prospect in the field of osteoporotic bone defect repair.

The invention relates to the technical field of osteoclast differentiation inhibitors, and discloses application of a quinoxalinone compound in preparation of an osteoclast differentiation inhibitor. The quinoxalinone compound with the R group being the aliphatic nitrogen heterocyclic ring has no obvious cytotoxicity, can significantly inhibit expression of Trap and Ctsk genes in cells, and has a significant inhibition effect on formation of RANKL-induced osteoclasts. On the basis, the invention provides application of the quinoxalinone compound in preparation of an osteoclast differentiation inhibitor and a medicine for treating osteoporosis. Validation shows that the inhibiting effect is dose-dependent.

The application discloses a 2,3,4,9-tetrahydro-1H-pyridine [3,4-b] indole compound and a preparation method and application thereof. The 2,3,4,9-tetrahydro-1H-pyridine [3,4-b] indole compound is prepared from 3-hydroxy-4-methoxybenzaldehyde and 1-(chloromethyl)-2,6-difluorobenzene as starting materials through two-step reactions. The 1-(3-((2,6-difluorophenyl)oxy)-4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyridine [3,4-b] indole provided by the application has a significant inhibitory effect on RANKL-induced osteoclast differentiation and has no obvious cytotoxicity, and can be used as a novel candidate drug for inhibiting osteoclast differentiation and for targeted osteoclast treatment of bone mass loss related diseases.

An object of the present invention is to provide an effective and highly safe agent for inhibiting osteoclast differentiation, and a food or drink, pharmaceutical, supplement, and cosmetic that produce an osteoclast differentiation-inhibiting effect; and the object is fulfilled by an agent for inhibiting osteoclast differentiation, comprising a urolithin.