KR20180131964A - Pharmarceutical composition for preventiing or treating of bone related disorder - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for prevention or treatment of bone-related diseases, which promotes the differentiation of preosteoblasts into osteoblasts to induce the formation of calcified nodules and simultaneously suppresses the differentiation of myelocytes into osteoclasts and the function of osteoclasts, thereby effectively controlling bone homeostasis and being very useful for prevention or treatment of the bone-related diseases.

Description

[0001] PHARMACEUTICAL COMPOSITION FOR PREVENTION OR TREATING OF BONE RELATED DISORDER [0002]

The present invention relates to a pharmaceutical composition for prevention or treatment of bone related diseases.

Osteoporosis, which is a typical bone related disease, is a disease caused by imbalance in bone homeostasis of osteoclasts that absorb bone and osteoclasts that form bone, and is a skeletal disorder characterized by weakened bone strength, which may increase the risk of fracture (US NIH definition NIH, 2000).

This imbalance in bone homeostasis can be caused by aging, systemic diseases, menopause, and the like, which is a systemic disease in which the bone density is decreased and the microstructure of the bone tissue is degenerated to increase the risk of fracture. In other words, the disappearance of old bone and the generation of new bone are kept in balance, and bone density is maintained. Because new bone replacement is not smooth due to aging, menopause, etc., bone becomes loose and this process is repeated, The risk of quality becomes large.

Osteoporosis is a disease in which normal activity is maintained and the amount of bone required is reduced, for example, the amount of calcium in the bone is reduced. That is, the bone mineral density is reduced and the fracture is easily induced even in a light impact. The condition prior to the osteoporosis is referred to as osteopenia and refers to a state in which the thickness of the bone continues to become thinner and lighter until the hole is punctured. In addition, osteomalacia is a vitamin D deficiency or a large amount of calcium excretion in the case of kidney disease is not mixed with calcium in the bone bones in the state of the bones are bent to create a condition that means. In addition, bone atrophy refers to a reduction of bone degeneration, that is, a decrease in the bone mass of the already completed bone tissue.

Since the amount of bone in the human body is maintained through bone homeostasis by balancing osteoblasts and osteoclasts, it is important to develop therapeutic agents targeting molecules that play an important role in these cells. That is, when the activity of osteoclasts forming osteoblasts is decreased and the activity of osteoclasts absorbing bones is increased, diseases such as osteoporosis which is easily broken and thinning of bones are caused, (1996) 14: 59-64; Chad Deal, nature clinical practice RHEUMATOLOGY (2009) vol. 5 no 1; Kalervo Vaananen, Advanced Drug Delivery Reviews 57 (2005) 959-971). However, the currently marketed drugs for osteoporosis treatment are drugs that inhibit osteoclast activity except for parathyroid hormone, and development of drugs targeting osteoclasts is urgent.

On the other hand, cholesterol sulfate, which is a sterol sulfate, is one of constituent components of cell membranes, and exists at a high concentration in blood and skin. However, only a part of functions related to immune function and differentiation into skin cells have been revealed, My role has not been explicitly reported.

It is an object of the present invention to provide a pharmaceutical composition for preventing or treating a bone related disease comprising sterol sulfate as an active ingredient.

Another object of the present invention is to provide a food composition for preventing or ameliorating a bone related disease comprising sterol sulfate as an active ingredient.

However, the technical problem to be solved by the present invention is not limited to the above-mentioned problems, and other matters not mentioned can be clearly understood by those skilled in the art from the following description.

The present inventors have not reported a drug that increases osteoblast-induced osteoblast-induced bone resorption and osteoclast-induced bone resorption. As a result, they have found that sterol sulfate, especially [(2R) -6-methylheptan-2-yl] -2,3,4,7,8, < RTI ID = 0.0 & [(3S, 8S, 9S, 10R, 13R, 14S (4S) -8,10,10,10,10,10,11,12,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene- , 17R) -10,13-dimethyl-17 - [(2R) -6-methylheptan-2-yl] -2,3,4,7,8,9,11,12,14,15,16,17- dodecahydro-lH-cyclopenta [a] phenanthren-3-yl] hydrogen sulfate has a remarkable effect on the treatment and prevention of bone related diseases through the process of controlling bone homeostasis.

One embodiment of the present invention provides a pharmaceutical composition for preventing or treating a bone related disease comprising Sterol sulfate as an active ingredient.

In the present invention, the sterol is an abbreviation of steroidal alcohol and means an organic molecule of a steroid-based compound. It has been reported to be found in most plants, animals, and fungi, and can play an important physiological function in eukaryotic organisms, such as constituting membranes of animal cells or influencing fluidity, and acting as secondary signal transducers. For the purpose of the present invention, the sterol may be a sulphate of plant sterols Campesterol, Sitosterol, and Stigmasterol, and an animal sterol, cholesterol. Preferably, the sterol sulfate is cholesterol sulfate, and is a compound represented by the following formula (1): [(3S, 8S, 9S, 10R, 13R, 14S, 17R) -10,13- -Methylheptan-2-yl] -2,3,4,7,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthrene- (3S, 8S, 9S, 10R, 13R, 14S, 17R) -10,13-dimethyl-17 - [(2R) -6-methylheptan- , 7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-3-yl] hydrogen sulfate).

[Chemical Formula 1]

In another embodiment of the present invention there is provided a process for the preparation of [(3S, 8S, 9S, 10R, 13R, 14S, 17R) -10,13-dimethyl-17 - [(2R) -6- methylheptan- , [4S, 8S, 8S, 8S, 8S, 9S, 10R, 13R, 14S, 17R) -10,13-dimethyl-17 - [(2R) -6-methylheptan-2-yl] -2,3,4,7,8,9,11,12,14 , 15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-3-yl] hydrogen sulfate as an active ingredient.

In the present invention, the compound represented by Formula 1 is present at the same concentration as DHEAS (dehydroepiandrosterone sulfate), which is a steroid sulphate circulated in the human body, and protects red blood cells from osmotic dissolution as a constituent of the cell membrane, (J Lipid Res. 2003 Jul; 44 (7): 1268-78), as well as components that regulate cell adhesion, cell signaling, blood coagulation, fibrinolysis, and epidermal cell adhesion.

In the present invention, the bone-related diseases may be caused by the breakdown of the activity between osteoblasts, which play a role in bone formation in the body, and osteoclasts, which act to destroy bone.

In the present invention, the osteoclast is a large-sized polynuclear cell that destroys or absorbs bone tissue that is unnecessary in the process of bone growth. The mature osteoclast is a polynuclear cell and is formed by differentiating into hematopoietic stem cells. In addition, the osteoblasts differentiated from the mesenchymal stem cells survive for about 34 months, and the activated osteoclasts form new bone at the site where the old bone is degraded, and numerous osteoblasts form bone matrix to form bone matrix Is completed. After completion of the bone formation, about 70% or more of the osteoblasts are killed and some of them are differentiated into osteocytes and bone lining cells, and these homeostasis is continuously imbalanced Related diseases may occur.

Therefore, for the purpose of the present invention, the pharmaceutical composition comprising the sterol sulfate as an active ingredient has a role of promoting osteoblast differentiation and inhibiting osteoclast differentiation and function, unlike the pharmaceutical composition of the bone related diseases reported previously Can be performed simultaneously, thereby making it more effective in the treatment of bone related diseases.

Specifically, in the present invention, the bone related diseases are osteoporosis, osteomalacia, osteopenia, bone atrophy, fibrous dysplasia, Paget's disease, hypercalcemia, from the group consisting of hypercalcemia, neoplastic destruction, cancer-associated aggregate absorption disease, fracture, osteolysis, osteoarthritis, and rheumatoid arthritis. It may be one or more selected.

However, in the present invention, the osteoporosis may be one or more selected from the group consisting of primary osteoporosis due to aging, primary osteoporosis due to menopause, and primary osteoporosis due to oophorectomy. In addition, there is provided a method for treating osteoporosis, including osteoporosis, osteoporosis caused by glucocorticoid-induced osteoporosis, thyroid-induced osteoporosis, immobilization-induced osteoporosis, heparin-induced osteoporosis, immunosuppressive osteoporosis, renal osteoporosis, inflammatory osteoporosis, rheumatoid osteoporosis, And osteoporosis caused by a synthetic inhibitor.

In the present invention, the term "preventive " may include, without limitation, any action that inhibits symptoms caused by bone related diseases using the pharmaceutical composition of the present invention, or inhibits or delays the symptoms thereof.

Also, in the present invention, "treatment" may include, without limitation, any action that improves or alleviates symptoms caused by bone related diseases using the pharmaceutical composition of the present invention.

In the present invention, the pharmaceutical composition may be in the form of capsules, tablets, granules, injections, ointments, powders or beverages. The pharmaceutical composition may be a human.

The pharmaceutical composition of the present invention may be formulated into oral formulations such as powders, granules, capsules, tablets, aqueous suspensions, external preparations, suppositories, and sterilized injection solutions according to a conventional method, Can be used. The pharmaceutical compositions of the present invention may comprise a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier may be a binder, a lubricant, a disintegrant, an excipient, a solubilizing agent, a dispersing agent, a stabilizer, a suspending agent, a coloring matter, a perfume or the like in the case of oral administration. A solubilizing agent, an isotonic agent, a stabilizer and the like may be mixed and used. In the case of topical administration, a base, an excipient, a lubricant, a preservative and the like may be used. Formulations of the pharmaceutical compositions of the present invention may be prepared in various manners by mixing with pharmaceutically acceptable carriers as described above. For example, oral administration may be in the form of tablets, troches, capsules, elixirs, suspensions, syrups, wafers, etc. In the case of injections, they may be formulated in unit dosage ampoules or in multiple dosage forms have. Other, solutions, suspensions, tablets, capsules, sustained-release preparations and the like.

Examples of suitable carriers, excipients and diluents for formulation include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltoditol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil. Further, it may further include a filler, an anticoagulant, a lubricant, a wetting agent, a flavoring agent, an emulsifying agent, an antiseptic, and the like.

The route of administration of the pharmaceutical composition according to the present invention is not limited to the oral route, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, Sublingual or rectal. Oral or parenteral administration is preferred.

The term "parenteral" as used herein includes subcutaneous, intradermal, intravenous, intramuscular, intraarticular, intrasynovial, intrasternal, intrathecal, intralesional, and intracranial injection or infusion techniques. The pharmaceutical compositions of the present invention may also be administered in the form of suppositories for rectal administration.

The pharmaceutical compositions of the present invention may be administered to a variety of factors including the activity, age, body weight, general health, sex, diet, time of administration, route of administration, rate of excretion, drug combination and the severity of the particular disease to be prevented or treated, And the dose of the pharmaceutical composition may be appropriately selected by a person skilled in the art depending on the condition of the patient, the body weight, the degree of disease, the type of administration, the route of administration, and the period of time, and is preferably from 0.0001 to 10 g / kg or 0.001 to 10 g / kg. The administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way. The pharmaceutical composition according to the present invention can be formulated into pills, dragees, capsules, solutions, gels, syrups, slurries, suspensions.

Another embodiment of the present invention provides a food composition for preventing or ameliorating a bone related disease comprising Sterol sulfate as an active ingredient.

In another embodiment of the present invention, there is provided a food composition for preventing or ameliorating a bone related disease comprising the compound represented by the formula (1) as an active ingredient.

In the food composition of the present invention, the content of the sterol sulfate, bone related disease, formula (1), osteoporosis, and prevention is the same as that described in the pharmaceutical composition, and detailed description thereof will be omitted.

In the present invention, " improvement " may include, without limitation, any action that improves or alleviates symptoms caused by bone related diseases using the food composition of the present invention.

The food composition comprising the compound of the present invention as an active ingredient may be prepared in the form of various foods such as beverage, gum, tea, vitamin complex, powder, granule, tablet, capsule, have.

In the present invention, when the compound is included in the food composition, the amount thereof may be added in a proportion of 0.1 to 50% of the total weight, but is not limited thereto.

In the present invention, when the food composition is prepared in a beverage form, there are no particular limitations other than that the food composition is contained at the specified ratio, and it may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages . Specific examples of the natural carbohydrate include monosaccharides such as glucose and the like sugars such as polysaccharides such as disaccharides such as fructose and sucrose, dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol . Examples of the flavoring agent include natural flavoring agents (such as tau martin, stevia extract (for example, rebaudioside A and glycyrrhizin), and synthetic flavors (for example, saccharin and aspartame).

In the present invention, the food composition of the present invention may further contain flavoring agents such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants, pectic acid and its salts, alginic acid and its salts, , Protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like.

In the present invention, the above components can be used independently or in combination. The proportion of the additive is not critical to the present invention, but may be selected from the range of 0.1 to about 50 parts by weight per 100 parts by weight of the food composition of the present invention, but is not limited thereto.

The pharmaceutical compositions and food compositions containing the sterol sulfate according to the present invention as an active ingredient not only induces the formation of calcified nodules by promoting the differentiation of osteoclasts into osteoblast cells but also induces the differentiation of bone marrow cells into osteoclasts And effectively inhibits osteoclast function to effectively control bone homeostasis, and thus is very effective in preventing or treating bone related diseases.

FIG. 1 shows the results of confirming the degree of formation of osteoblast mineralized nodules by addition of the compound of formula 1, tauroowsodoxycholic acid, deoxycholic acid, or taurocholic acid according to an embodiment of the present invention.
FIG. 2 shows the results of confirming the degree of formation of mineralized nodule due to addition of the chemical formula 1 according to an embodiment of the present invention.
FIG. 3 shows the results of confirming the degree of formation of osteoblast mineralized nodule due to addition of taurosoldoxyocholic acid, deoxycholic acid, or taurocholic acid according to an embodiment of the present invention.
FIG. 4 shows the results of confirming the expression of the differentiation marker gene of osteoblast according to an embodiment of the present invention.
FIG. 5 shows the results of confirming the degree of differentiation of bone marrow cells into osteoclasts according to an embodiment of the present invention.
FIG. 6 shows the results of the functional evaluation of osteoclasts according to an embodiment of the present invention.

Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are illustrative of the present invention, and the contents of the present invention are not limited by the following examples.

Example

[Preparation Example 1] Preosteoblast cell and bone marrow cell separation

Preosteoblast cells and bone marrow cells were isolated from rats in order to confirm the bone homeostasis effect of the compounds according to the present invention.

In order to isolate the osteoclasts, two calvaria of 1 to 3 days old rats were collected and treated with 1 mg / ml collagenase and 2 mg / ml dispase, Bone cells were obtained.

In order to isolate the bone marrow cells, the tibia and femur of 4 to 6 week old male rats are separated, and then the both ends of the bone are cut and the cells are extracted from the middle part. Cells were obtained.

[Example 1] Measurement of calcified nodules of osteoblasts

It was confirmed by the compound according to the present invention that the osteoblast significantly promotes the mineralized nodule.

The pre-osteoclasts obtained in Preparation Example 1 were dispensed into a 12-well cell culture plate in an amount of 0.5 × 10 ⁵ cells / well, and fetal bovine serum (FBS) corresponding to 10% of the medium volume and 1 The cells were cultured on? -MEM medium containing penicillin-streptomycin, 50 μg / ml L-ascorbic acid, and 10 mM β-glycerophosphate. In the same manner as the compound of the present invention or the compound of the present invention, taurosoldoxyocholic acid, deoxycholic acid, or taurocholic acid is added as a compound derived from bile acid at a concentration of 0 to 50 μM, Differentiation was induced. However, the medium for inducing the differentiation was replaced with fresh medium at intervals of 2 to 3 days, and the differentiation was induced for a total of 21 days. Alizarin red staining was performed to confirm the differentiation of the differentiated osteoblasts. Cells with differentiation induction were cultured in 10% neutral formalin for 20 min at 4 ° C. and then stained with alginate red solution of 1.36% and pH 4.1-4.3 for 40 min. The results are shown in Fig. As a result, the amount of pigment stained in the nodule was increased as the treatment concentration was increased from 15 μM to 35 μM as compared with the negative control (0 μM) in which the compound of the present invention was added . However, the precursor bone cells supplemented with taurosoldoxyoylic acid, deoxycholic acid, or taurocholic acid, which is classified as a compound derived from bile acid in the same manner as in Chemical Formula 1, It was not found at all. This means that the compound of formula (I) of the present invention specifically has an osteogenic differentiation effect among the compounds derived from bile acid.

In order to quantitatively evaluate the degree of differentiation of osteoclasts to which the compound of formula (1) was added, the coloring matter of the nodule was extracted with 10% of cetylpyridinium chloride, and the absorbance at 570 nm was measured. Respectively. As a result, the OD value was about 0.5 at 10 μM, while it was about 3 at 35 μM and about 3 at 40 μM, indicating that the osteogenic differentiation effect was increased in a concentration dependent manner in the range of 10 to 45 μM.

The results of quantitative determination of taurourosoldoxycholic acid, deoxycholic acid, or taurocholic acid are shown in FIG. Consistent with the image of Figure 1, there was no significant difference in quantitation compared to negative control (0 [mu] M).

[Example 2] Measurement of osteoblast differentiation

In order to confirm whether the precursor bone cells promote osteoblast differentiation by the compound according to the present invention, the expression of the differentiation marker gene of osteoblast was confirmed.

In the same manner as in Example 1 except that 25 μM of [(3S, 8S, 9S, 10R, 13R, 14S, 17R) -10,13-dimethyl-17 - [(2R) -6- methylheptan- , [4S, 8S, 8S, 8S, 8S, 9S, 10R, 13R, 14S, 17R) -10,13-dimethyl-17 - [(2R) -6-methylheptan-2-yl] -2,3,4,7,8,9,11,12,14 , 15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-3-yl] hydrogen sulfate, and cultured for 15 days to induce differentiation of osteoclasts using RNeasy Mini (QIAGEN) The total RNA (total RNA) of each RNA was extracted by the protocol presented in the kit. The total RNA (total RNA) of each RNA was extracted. 2 μg of the extracted RNA was reacted with RevertAid Revert Transcriptase (Thermo Scientific, USA) at 42 for 1 hour to obtain cDNA. Then, using SensiFAST ^™ SYBR Hi-ROX Kit (Bioline) Real-time PCR was performed. Specific reaction conditions were denatured at 95 for 3 minutes, followed by 40 cycles of 95 to 5 seconds, 60 to 10 seconds, and 72 to 15 seconds. The quantitative results are shown in FIG.

As shown in FIG. 4, gene expression of Sp7, Bgiap, and Ibsp, genes corresponding to the differentiation markers of osteoblast, was significantly different from that of the control (OS) by more than 2 times.

From the above results, it can be seen that the compound according to the present invention not only remarkably increases the amount of calcified nodules generated in osteoblasts but also promotes differentiation of osteoclasts into osteoblasts.

[Example 3] Measurement of osteoclast differentiation

It was confirmed that osteoclast differentiation was remarkably inhibited by the compound according to the present invention.

The bone marrow cells obtained in Preparation Example 1 were dispensed in a number of 5 × 10 ⁴ cells / well on a 96-well cell culture plate, and fetal bovine serum (FBS) corresponding to 10% of the medium volume and 1% (3S, 8S, 9S, 10R, 13R, 14S, 17R) -10 (10 mg / ml) was added to? -MEM medium containing penicillin-streptomycin, 30 ng / ml of M-CSF and 50 ng / ml of RANKL. , 13-dimethyl-17- [(2R) -6-methylheptan-2-yl] -2,3,4,7,7,8,9,11,12,14,15,16,17-dodecahydro- ([(3S, 8S, 9S, 10R, 13R, 14S, 17R) -10,13-dimethyl-17 - [(2R) -6 -methylheptan-2-yl] -2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-3-yl] hydrogen sulfate) The concentration of 0 ~ 25 μM was added to induce osteoclast differentiation. However, the medium for inducing the differentiation was replaced with a fresh medium at intervals of 2 days, and the differentiation was induced for a total of 4 to 5 days.

In order to confirm the degree of differentiation of the differentiated bone marrow cells, the TRAP staining kit (Sigma Aldrich, USA) was used to stain the cells by the protocol shown in FIG. 5, The results are shown in Fig.

As shown in FIG. 5 and FIG. 6, the bone marrow cells were inhibited from osteoclast differentiation, and when the concentration of the compound according to the present invention was 6.25 μM and 12.5 μM, the function was inhibited by about 0.2 compared to the negative control, At 25 μM, the function was inhibited by about 0.3.

(3S, 8S, 9S, 10R, 13R, 14S, 17R) -10,13-dimethyl-17 - [(2R) -6- methylheptan- ([(3S, 8S) -7- , 9S, 10R, 13R, 14S, 17R) -10,13-dimethyl-17 - [(2R) -6-methylheptan-2-yl] -2,3,4,7,8,9,11,12, 14,15,16,17-dodecahydro-1H-cyclopenta [a] phenanthren-3-yl] hydrogen sulfate inhibits the differentiation of bone marrow cells into osteoclasts as well as inhibits osteoclast function have.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the scope of the present invention is not limited to the disclosed exemplary embodiments, but various changes and modifications may be made without departing from the scope of the invention. It will be obvious to those who have knowledge of

Claims (18)

A pharmaceutical composition for preventing or treating a bone related disease comprising Sterol sulfate as an active ingredient.
The method according to claim 1,
Wherein the sterol is at least one selected from the group consisting of Campesterol, Sitosterol, Stigmasterol, and Cholesterol.
The method according to claim 1,
Wherein the sterol sulfate is represented by the following formula 1:
[Chemical Formula 1]

The method according to claim 1,
Wherein said pharmaceutical composition promotes the differentiation of precursor bone cells into osteoblasts.
The method according to claim 1,
Wherein said pharmaceutical composition inhibits the differentiation of bone marrow cells into osteoclasts.
The method according to claim 1,
The bone-related diseases include, but are not limited to, osteoporosis, osteomalacia, osteopenia, bone atrophy, fibrous dysplasia, Paget's disease, hypercalcemia, At least one member selected from the group consisting of neoplastic destruction, cancer-associated aggregate absorption disease, fracture, osteolysis, osteoarthritis, and rheumatoid arthritis ≪ / RTI >
The method according to claim 6,
Wherein the osteoporosis is at least one selected from the group consisting of primary osteoporosis by aging, primary osteoporosis by menopause, and primary osteoporosis by oophorectomy.
The method according to claim 6,
The osteoporosis may be selected from the group consisting of glucocorticoid-induced osteoporosis, thyroid glandular osteoporosis, fixed-induced osteoporosis, heparin-induced osteoporosis, immunosuppressive osteoporosis, osteoporosis due to renal failure, osteoporosis due to Cushing's syndrome, rheumatoid osteoporosis, And osteoporosis by an estrogen synthesis inhibitor.
The method according to claim 1,
Wherein the sterol sulfate is contained at a concentration of 10 to 100 [mu] M.
A food composition for preventing or ameliorating a bone related disease comprising Sterol sulfate as an active ingredient.
11. The method of claim 10,
Wherein the sterol is at least one selected from the group consisting of Campesterol, Sitosterol, Stigmasterol, and Cholesterol.
11. The method of claim 10,
Wherein the sterol sulfate is represented by the following formula 1:
[Chemical Formula 1]

11. The method of claim 10,
Wherein the food composition promotes the differentiation of osteoclasts into osteoclasts.
11. The method of claim 10,
Wherein said food composition inhibits the differentiation of bone marrow cells into osteoclasts.
11. The method of claim 10,
The bone-related diseases include, but are not limited to, osteoporosis, osteomalacia, osteopenia, bone atrophy, fibrous dysplasia, Paget's disease, hypercalcemia, At least one member selected from the group consisting of neoplastic destruction, cancer-associated aggregate absorption disease, fracture, osteolysis, osteoarthritis, and rheumatoid arthritis , ≪ / RTI >
A composition for promoting bone regeneration comprising Sterol sulfate as an active ingredient.
17. The method of claim 16,
Wherein the sterol is at least one selected from the group consisting of campesterol, sitosterol, stigmasterol, and cholesterol.
17. The method of claim 16,
Wherein the sterol sulfate is represented by the following formula 1:
[Chemical Formula 1]

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