222 results about "Osteocyte" patented technology

The invention belongs to the technical field of microbial fermentation, and particularly relates to lactobacillus rhamnosus capable of maintaining bone health and improving local joint inflammation and a metagen and application of the lactobacillus rhamnosus. According to the invention, the probiotic NKU ML1-2 is subjected to fermentation culture, such that a post-generation product is prepared. Results of embodiments prove that the metagen product can enhance the oxidation resistance of cartilage and osteoblasts and promote the synthesis of anti-inflammatory factors and cartilage matrixes (type II collagen and proteoglycan), and has the potential of relieving oxidative stress and inflammatory response of local joints, relieving joint inflammation and delaying cartilage destruction. The prepared metagen product is high in safety and good in stability, and can be applied to preparation of medicines for preventing and / or treating osteoarthritis; the metagen product can also be used for promoting bone health, enhancing the antioxidant capacity of osteoblasts and / or chondrocytes, promoting osteoblast activity and / or promoting calcium absorption and fixation, and a new solution is provided for joint health management.

The invention provides modified milk powder capable of promoting bone health as well as a preparation method and application of the modified milk powder. The total protein content of the modified milk powder is 17-35 g / 100 g, the fat content of the modified milk powder is 1-32 g / 100 g, and the calcium content of the modified milk powder is 0.8-2.1 g / 100 g. Moreover, the modified milk powder contains bovine coloctrum and lactoferrin, the mass ratio of the bovine coloctrum to the lactoferrin is (5-100): 1 on the basis of the dry matter content, and the content of the lactoferrin in the modified milk powder is 2-400 mg / 100 g. The bovine colostrum and the lactoferrin are combined for preparing the milk powder, have a synergistic effect on promoting osteoblasts and inhibiting osteoclast proliferation, and are beneficial to bone health.

The invention relates to a diatomic iron-iron site nano-enzyme constructed by relieving oxidative stress and cartilage degeneration and used for targeted osteoarthritis treatment. According to the invention, a nitrogen-doped porous carbon anchored diatomic iron nano enzyme catalyst (Fe2-NCs) with Fe-Fe dimer coordination is developed by using a'subject-object 'strategy. The Fe2-NCs protect cartilage cells from oxidative stress induced apoptosis by modulating ROS and active nitrogen species (RNS) and promoting O2 release. In addition, Fe2-NCs restores mitochondrial function by inhibiting NOX4 expression, improving ATP production, and normalizing COXIV levels. In an in-vivo OA model, the Fe2-NCs can reduce the expression of a pro-inflammatory medium COX-2 through an NF-kappa B signal channel, inhibit the up-regulation of MMP-13 and delay the degradation of type II collagen. The invention provides a new theoretical framework and methodological approach for the treatment of osteoarthritis, and has important clinical and scientific significance.

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 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 present invention relates to lipid nanoparticle (LNP) compositions, as well as diagnostic or therapeutic polynucleotides, such as TERT mRNA, that can be delivered in a formulation together with the LNP compositions to various tissue and cell types in the whole body of a mammal, such as, for example, TNP mRNA. Comprising stem cells, progenitor cells, germ cells, differentiated cells or terminally differentiated cells, cancer cells, endothelial cells, epithelial cells, splenic cells, hepatocells, kidney cells and / or osteoblasts, for example, for use in the diagnosis, prevention and / or treatment of a condition or disease.

The invention provides a composition for changing plasticity of bone meal particles as well as a preparation method and application of the composition, and relates to the technical field of biomedical materials. The composition is prepared from the following raw material components: bioactive glass, dihydrazide modified sodium hyaluronate, sodium hyaluronate with the molecular weight of 50kDa to 500kDa, a polylactic acid-glycolic acid copolymer and carboxymethyl cellulose. The preparation method of the dihydrazide modified sodium hyaluronate comprises the following steps: carrying out carboxyl activation on sodium hyaluronate, carrying out a cross-linking reaction on the activated hyaluronic acid and adipic dihydrazide, and then terminating the reaction. The composition provided by the invention not only can provide support, but also can adjust the degradation rate to be matched with the bone regeneration period, and all the components synergistically improve the mechanical property and the viscoelastic property. The composition disclosed by the invention can be formed in situ at a bone defect part, provides a space for growth and proliferation of bone cells, improves the biological activity and osteoinductivity of an artificial bone, and promotes bone growth and repair.

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 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 application discloses a cell-penetrating peptide-oligonucleotide delivery system prepared based on a biological orthogonal click chemical reaction and a preparation method and application thereof. The cell-penetrating peptide with a cell membrane penetration function and the oligonucleotide with a biological function are connected through the biological orthogonal click chemical reaction, so that the biological activity of the biomolecule can be better maintained, a high fidelity is provided for a wide range of functional groups, no obvious toxic side effects are caused, and the oligonucleotide delivery is efficiently realized, thereby providing a new approach for preventing and treating osteoclast activation diseases.

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.

Embodiments of the disclosure include methods and compositions related to modulation of bone using particular fibroblasts. The modulation includes reducing osteoclast activity and / or activation and / or stimulating osteoblast activity. In particular cases, bone is modulated in an individual with a bone condition, such as osteoporosis. Particular fibroblasts may be delivered to reduce inflammatory cytokine production including RANK ligand.

The application discloses a 3D-printed intervertebral fusion cage, which is used to solve the problem of poor bone ingrowth effect of the prior art fusion cage, slow degradation speed, and early release of active ingredients, and the structure comprises a frame and an embedded pipe, the embedded pipe is arranged in the frame, the components are all made of degradable metal materials and can be gradually degraded in the human body, the embedded pipe is further encapsulated with active ingredients for promoting bone growth, and the active ingredients are released with the degradation of the embedded pipe, so that the early release of the drugs in the embedded pipe is avoided, long-acting effect is achieved, and of course a net beam is arranged in the gap of the frame, and the porous structure formed by the net beam further increases the bone ingrowth effect; the application creatively uses a 3D process to realize the encapsulation of the active ingredients and the forming of the porous support, and is combined with the degradable metal to realize the sustained release, so that a good growth condition is provided for the bone ingrowth in the porous support, the effect of the growth factors is fully played, and the treatment effect is improved.

The invention relates to an ROS-responsive macrophage-chondrocyte dual-targeting nano-micelle and a preparation method and application thereof, HA capable of targeting and highly expressing CD44 cells is taken as a carrier skeleton, chemical coupling with TK and CUR is carried out in sequence, self-assembly is carried out through intermolecular force to form a stable nano-micelle, and drugs JPH203 and KGN are entrapped at the same time, so that efficient loading and targeting delivery are realized. The HA can be specifically combined with RAW264.7 macrophages and articular cartilage cells for highly expressing a CD44 receptor in an inflammatory state, and is actively delivered in a targeting manner. The ROS response characteristic of TK is utilized, oxidative fracture is carried out in an OA high ROS microenvironment, and micelles are triggered to disintegrate and release drugs accurately. The released JPH203 can inhibit an inflammatory mTOR pathway and effectively resist inflammation, and KGN is beneficial to promoting cartilage cell proliferation and effectively collecting and promoting differentiation of mesenchymal stem cells into cartilage cells, so that in-situ cartilage regeneration is realized, and a more efficient solution with low side effects is provided for osteoarthritis treatment.

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 a mesenchymal stem cell medicine for promoting knee joint cartilage regeneration as well as a preparation method and application thereof, and belongs to the technical field of medicines. The preparation method comprises the following steps: reacting polyethyleneimine with linoleoyl chloride to prepare linoleoyl chloride modified polyethyleneimine for preparing curcumin lipidosome, and reacting with multifunctional peptide to prepare multifunctional lipidosome; the mesenchymal stem cells are mixed with self-assembled RADA16 polypeptide embedded with TGF-beta1 and BMP-6 and subcultured mesenchymal stem cells, the mixture is added into autologous platelet-enriched plasma, and the mesenchymal stem cell medicine for promoting knee joint cartilage regeneration is prepared. According to the invention, curcumin is embedded by lipidosome, mesenchymal stem cells can promote osteogenesis differentiation by using provided nutrients, and interference of inflammatory microenvironment is effectively prevented. Meanwhile, the self-assembled RADA16 polypeptide wraps TGF-beta1 and BMP-6, the synergistic effect is beneficial to regeneration and repair of cartilage tissue, proliferation of bone cells is promoted, and cartilage repair and regeneration are facilitated.

[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.

This invention relates to the field of biomedical materials, providing non-denatured type II collagen ultrafine powder with cartilage tissue-targeted growth and structural repair functions, its bioactivity preservation preparation method, and its application in joints. The ultrafine powder has an average particle size of 0.5-50 μm, a triple helix structure integrity rate of not less than 85%, a thermal denaturation temperature of 38-48℃, and retains chondrocyte binding domains CB10, CB11, and MMP cleavage sites. The preparation method includes raw material pretreatment, time-limited enzymatic hydrolysis, graded purification, and ultra-low temperature ball milling. The product can be used for the repair and treatment of cartilage degenerative diseases such as osteoarthritis and cartilage damage.

The invention belongs to the technical field of biological medicine, and particularly relates to a small-molecule exosome-loaded composition based on bone marrow mesenchymal stem cells and application of the small-molecule exosome-loaded composition. The invention discloses the treatment effect of squalene on osteoarthritis for the first time, and further prepares the squalene-loaded bone marrow mesenchymal stem cell exosome. An in-vitro cell experiment and a model animal experiment prove that the composition has a synergistic treatment effect on osteoarthritis. In-vitro tests prove that the squalene-loaded mesenchymal stem cell exosome can improve the survival rate of inflammatory cartilage cells, inhibit release of proinflammatory factors and restore expression of repair factors. Model animal experiments prove that the squalene-loaded mesenchymal stem cell exosome has the effects of resisting inflammation, easing pain and protecting cartilage in the treatment of osteoarthritis.

The invention belongs to the technical field of microorganisms, and particularly relates to application of bifidobacterium animalis subsp. Lactis in improvement of osteoporosis. The bifidobacterium animalis subsp. Lactis BL-136 provided by the invention is preserved in Guangdong Microbial Culture Collection Center, the preservation number is GDMCC No: 67831, and verification proves that the strain has excellent capability of inhibiting osteoclast differentiation and has obvious application advantages in the aspect of relieving osteoporosis. The microgel preparation prepared from the strain can play an excellent role in relieving the osteoporosis, and the curative effect on the osteoporosis is remarkably improved. Therefore, the invention proves the curative effect of the bifidobacterium animalis subsp. Lactis BL-136 and the microgel preparation thereof in the aspect of relieving the osteoporosis, and scientific thinking and technical support can be provided for the development of medicines for treating the 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 invention discloses an injectable hydrogel pharmaceutical composition for an articular cavity as well as a preparation method and application of the injectable hydrogel pharmaceutical composition. The hydrogel pharmaceutical composition comprises gel particles and a medicine loaded in the gel particles, the gel particles are formed by cross-linking hyaluronic acid or salt thereof and silk fibroin through a cross-linking agent; the medicine comprises an anti-inflammatory drug and / or a growth factor. The preparation method is simple, good in safety and beneficial to industrial production. The uniform porous structure of the hydrogel is beneficial to adhesion and growth of bone cells, meanwhile, the double-load hydrogel loaded with the anti-inflammatory drug and the growth factor has good viscoelasticity and injectability and has the effects of synergistically resisting inflammation and promoting cartilage repair, and bone joint related diseases are treated in a bone joint intracavity injection mode; the drug residence time can be prolonged, and the bioavailability is improved.

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.

This invention belongs to the field of biomedical technology, specifically relating to the application of bufalin in the preparation of drugs for treating osteoarthritis. The structure of bufalin is shown in the following formula. Research results of this invention show that bufalin can significantly inhibit the inflammatory response and matrix degradation of chondrocytes, protecting the extracellular matrix of chondrocytes, thereby effectively delaying or reversing the pathological progression of osteoarthritis. This invention uses the SW1353 human chondrosarcoma cell line and SD rat primary chondrocytes as in vitro experimental models. The two cell models mutually validated each other, fully demonstrating the protective effect of bufalin on chondrocytes and its potential application value in the treatment of osteoarthritis.

The invention belongs to the technical field of food-borne functional factors, and particularly relates to a bioactive glycopeptide as well as a preparation method and application thereof. According to the application, casein glycomacropeptide is taken as a substrate, specific protease is adopted for carrying out directional enzymolysis reaction on the casein glycomacropeptide, and after primary separation and purification by hydrophilic interaction chromatography and secondary purification by cation exchange chromatography are carried out, the bioactive glycopeptide with the molecular weight of less than 1,500 Da and more than 80% of components and the random coil secondary structure content of more than 35% is obtained. A system performance test shows that in an in-vitro cell experiment, the bioactive glycopeptide prepared by the embodiment of the invention can remarkably improve the proliferation rate of preosteoblasts and lay a sufficient cell quantity foundation for bone cell generation; meanwhile, the activity of an osteogenic early differentiation key marker ALP is effectively up-regulated, and the differentiation process of preosteoblasts towards the osteoblast direction is accelerated; in addition, the expression quantity of osteogenesis-related regulatory protein calcium-sensitive receptors is remarkably increased, and the function improvement of cells to mature bone cells is further promoted.

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.