Bone differentiation promoter and bone formation promoter

Abstract

To provide a novel bone differentiation promoter and a bone formation promoter, and to further provide a preventive agent against osteoporosis and a preventive agent against locomotive syndrome.SOLUTION: The present invention provides a bone differentiation promoter and a bone formation promoter comprising sebacic acid or a salt thereof; a preventive agent against osteoporosis comprising the bone formation promoter; and a preventive agent against locomotive syndrome comprising the preventive agent against osteoporosis.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to an agent for promoting bone differentiation and an agent for promoting bone formation. Further, the present invention relates to a preventive agent for osteoporosis and a preventive agent for locomotive syndrome.

Background Art

[0002] Bone is constantly regenerated while maintaining dynamic homeostasis by the delicate balance between destruction and formation. This reconstruction, called bone remodeling, begins with a series of processes in which osteoclasts absorb (destroy) old bone (resorption phase). Next, the old osteoclasts are phagocytosed by macrophages and the function of osteoclasts is suppressed (reversal phase), and osteoblasts secrete and fill the bone matrix in the missing part (formation phase). After the bone is replenished by bone formation by osteoblasts, bone formation is arrested (quiescent phase). Thus, the balance between bone destruction and formation is strictly regulated by both osteoblasts responsible for bone formation and osteoclasts responsible for bone resorption. When this balance is disrupted, bone tissue becomes abnormal and is known to exhibit various bone diseases such as osteoporosis.

[0003] Currently, bisphosphonate preparations and the like are used as therapeutic agents for osteoporosis. However, there are still problems that have not been solved in terms of treatment efficiency and safety, and the development of further therapeutic agents that solve these problems is required. In particular, from the viewpoint of daily use, a material that can be used in both foods and pharmaceuticals is desirable.

[0004] Royal jelly is a milky substance synthesized in the salivary glands of honeybees and secreted from the mandibular glands in the head. It is given by worker bees to larvae placed in queen bee cells to make queen bees. Currently, royal jelly is widely used around the world in health foods, pharmaceuticals, cosmetics, etc. As its effectiveness, an increase in blood flow, a blood pressure lowering effect, a growth promoting effect, a sex hormone-like effect, an antibacterial effect, an antitumor effect, a wound healing promoting effect, an autonomic nerve disorder healing effect, an anti-stress effect, a calcium absorption promoting effect, a blood glucose level lowering effect, an antioxidant effect, etc. have been reported.

[0005] In Non-Patent Document 1, it is reported that in a clinical trial involving 72 postmenopausal women, the decrease in bone mineral density and the decrease in the expression of bone formation markers observed in the placebo group were alleviated by royal jelly intake.

[0006] In Non-Patent Document 2, it was reported that the decrease in bone mineral density was suppressed by royal jelly intake in menopause model mice, and that the differentiation into osteoclasts was suppressed when royal jelly and 10-hydroxy-2-decenoic acid were added under osteoclast differentiation induction conditions for mouse-derived bone marrow cells containing mesenchymal stem cells.

[0007] In Patent Document 1, it is reported that straight-chain fatty acids having 10 carbon atoms such as 10-hydroxydecanoic acid and 10-hydroxy-2-decenoic acid or salts thereof exhibit estrogen-like effects, and that these are used as active ingredients of osteoporosis preventive agents.

Prior Art Documents

Patent Documents

[0008]

Patent Document 1

Non-Patent Documents

[0009]

Non-Patent Document 1

Non-Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0010] However, in none of Non-Patent Documents 1 and 2 and Patent Document 1 has the bone differentiation promoting effect of sebacic acid been confirmed or reported.

[0011] The present invention aims to provide a novel bone differentiation promoter and a bone formation promoter. Further, the present invention aims to provide a preventive agent for osteoporosis and a preventive agent for locomotive syndrome.

Means for Solving the Problems

[0012] The inventors of the present invention conducted intensive studies to achieve the above object, and found that sebacic acid, which is a metabolite of decanoic acid contained in royal jelly, has an action of promoting bone differentiation through bone marrow-derived mesenchymal stem cells, and completed the present invention. This functionality of sebacic acid leads to the alleviation and prevention of age-related symptoms such as osteoporosis and locomotive syndrome.

[0013] That is, the present invention relates to the following [1] to [6]. [1] A bone differentiation promoter containing sebacic acid or a salt thereof. [2] The bone differentiation promoter according to [1], which has an action of activating the expression of Runx2 dependent on the Wnt / β-catenin signaling pathway in mesenchymal stem cells in the bone marrow. [3] A bone formation promoter containing sebacic acid or a salt thereof. [4] A preventive agent for osteoporosis containing the bone formation promoter according to [3]. [5] A preventive agent for locomotive syndrome containing the preventive agent for osteoporosis according to [4]. [6] The agent according to any one of [1] to [5], which is a food or drink, a pharmaceutical product, or a quasi-drug.

Effects of the Invention

[0014] Since sebacic acid contained in royal jelly has an action of promoting bone differentiation, it is useful as an active ingredient of a bone differentiation promoter, a bone formation promoter, a preventive agent for osteoporosis, and a preventive agent for locomotive syndrome.

Brief Description of the Drawings

[0015]

Figure 1

Figure 2

Figure 3

Mode for Carrying Out the Invention

[0016] Hereinafter, the embodiments for carrying out the present invention will be described in detail, but the present invention is not limited to the following embodiments.

[0017] In this specification, "comprise" includes the meanings of "essentially consist of" and "consist of only".

[0018] In the present invention, promoting osteogenic differentiation means, for example, promoting the differentiation of bone marrow-derived mesenchymal stem cells into osteoblasts, the calcification of osteoblasts, etc. Osteoblasts are cells that form bone in bone tissue and have the ability to calcify. Osteoblasts can be alkaline phosphatase positive, have staining properties in alizarin red staining, and / or be osteocalcin positive.

[0019] The osteogenic differentiation promoter and osteogenesis promoter of the present invention are characterized by containing sebacic acid or a salt thereof as an active ingredient.

[0020] Here, sebacic acid is one of the fatty acids represented by the following formula.

[0021]

Chemical formula

[0022] Sebacic acid is one of the fatty acids contained in royal jelly. Also, sebacic acid is formed from 10-hydroxydecanoic acid when it is metabolized in the body. 10-Hydroxydecanoic acid is also one of the fatty acids contained in royal jelly. Sebacic acid or its salt may be a synthetic product, or may be a natural product such as one derived from royal jelly. Sebacic acid derived from royal jelly can be obtained, for example, by extraction and purification from royal jelly using an organic solvent or the like. Sebacic acid or its salt can be purified according to methods commonly used by those skilled in the art after synthesis or extraction. The purification method is not particularly limited, and examples include precipitation methods, liquid-liquid countercurrent distribution methods, adsorption treatments using activated carbon, resins, etc., purification treatments using column chromatography, ion exchange chromatography, etc. Note that the isolation and purification of sebacic acid or its salt do not need to be carried out up to a purity of 100% by mass. The sebacic acid or its salt used in the present invention may have a purity of usually 50% by mass or more, preferably 80% by mass or more, more preferably 90% by mass or more.

[0023] In the present invention, either sebacic acid or its salt in a non-isolated or non-purified state (crude extract) and an isolated or purified one can be used.

[0024] The salts of sebacic acid are not particularly limited, and examples thereof include alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt; ammonium salt; aliphatic amine salts such as trimethylamine salt, triethylamine salt, cyclohexylamine salt, ethanolamine salt, diethanolamine salt, triethanolamine salt, and procaine salt; aralkylamine salts such as N,N-dibenzylethylenediamine; heterocyclic aromatic amine salts such as pyridine salt, picoline salt, quinoline salt, and isoquinoline salt; quaternary ammonium salts such as tetramethylammonium salt, tetraethylammonium salt, benzyltrimethylammonium salt, benzyltributylammonium salt, methyltrioctylammonium salt, and tetrabutylammonium salt; amino acid salts such as arginine salt, lysine salt, histidine salt, arginine salt, aspartate salt, and glutamate salt; inorganic acid salts such as hydrochloride, sulfate, nitrate, phosphate, carbonate, hydrogen carbonate, and perchlorate; organic acid salts such as acetate, propionate, lactate, maleate, fumarate, tartrate, malate, citrate, and ascorbate; sulfonate salts such as methanesulfonate, isethionate, benzenesulfonate, and p-toluenesulfonate, etc.

[0025] Royal jelly is a milky jelly-like substance made by mixing the secretions secreted from the hypopharyngeal gland and the major salivary gland of worker bees aged 3 to 12 days among honeybees. The royal jelly in the present invention includes raw royal jelly, dried royal jelly, dried royal jelly powder, enzyme-treated royal jelly, royal jelly extract, royal jelly fermented product, etc. Also, the production area of royal jelly may be any of European countries, Oceania countries, the United States, Brazil, Japan, China, and other Asian countries, etc.

[0026] Dried royal jelly powder is obtained by drying raw royal jelly and pulverizing it.

[0027] As drying methods, any known methods employed in general food processing can be used, such as natural drying like ventilation drying or sun drying, forced drying by heating with electricity or the like, and freeze drying. Preferably, it is freeze drying.

[0028] Enzyme-treated royal jelly is obtained by treating royal jelly with a proteolytic enzyme (protease). The royal jelly used for the production of enzyme-treated royal jelly is not particularly limited, and examples include raw royal jelly, royal jelly powder obtained by drying raw royal jelly into a powder, or an extract obtained by extracting raw royal jelly with water or hydrous ethanol or the like.

[0029] The production of enzyme-treated royal jelly can be carried out by treating a royal jelly raw material with at least an enzyme having an endopeptidase action, at least an enzyme having an exopeptidase action, and / or an enzyme having both an endopeptidase action and an exopeptidase action.

[0030] Examples of proteolytic enzymes having at least endopeptidase activity include endopeptidases derived from animals (e.g., trypsin, chymotrypsin, etc.), plants (e.g., papain, etc.), and microorganisms (e.g., lactic acid bacteria, yeast, mold, Bacillus subtilis, actinomycetes, etc.).

[0031] Examples of proteolytic enzymes having at least exopeptidase activity include carboxypeptidase, aminopeptidase, exopeptidases derived from microorganisms (e.g., lactic acid bacteria, Aspergillus spp., Rhizopus spp., etc.), pancreatin having endopeptidase activity as well, pepsin, and the like.

[0032] Among such various enzymes, preferred examples of enzymes having both exopeptidase activity and endopeptidase activity include peptidase produced by Streptomyces griseus (trade name: Actinase AS), peptidase produced by Aspergillus oryzae (trade names: Protease A, Flavorzyme, Proteax), peptidase produced by Aspergillus melleus (trade name: Protease P). Also, preferred examples of enzymes having exoprotease activity include peptidase produced by Aspergillus oryzae (trade names: Umamizyme G, Promod 192P, Promod 194P, Sumitzyme FLAP), peptidase produced by Aspergillus sojae (trade name: Sternzyme B15024), peptidase produced by Aspergillus genus (trade name: Kokurase P), peptidase produced by Rhizopus oryzae (trade name: Peptidase R). Further, preferred examples of enzymes having endoprotease activity include peptidase produced by Bacillus subtilis (trade names: Orientase 22BF, Nuclein), peptidase produced by Bacillus licheniformis (trade name: Alcalase), peptidase produced by Bacillus stearothermophilus (trade name: Protease S), peptidase produced by Bacillus amyloliquefaciens (trade name: Neutrase), peptidase produced by Bacillus genus (trade name: Protamex).

[0033] Royal jelly extract is obtained by extracting royal jelly (including raw, dried, and pulverized products) with water or hydrous ethanol or the like.

[0034] The royal jelly ferment can be produced by a conventional method using microorganisms such as yeast and lactic acid bacteria.

[0035] Commercially available royal jelly can be used.

[0036] The bone differentiation promoter and bone formation promoter of the present invention may consist only of sebacic acid or a salt thereof, or may contain only sebacic acid or a salt thereof as an active ingredient. Further, the bone differentiation promoter and bone formation promoter of the present invention may contain other components as long as the bone differentiation promoting action of sebacic acid or a salt thereof is not hindered. The content of sebacic acid or a salt thereof in the bone differentiation promoter and bone formation promoter is, based on the total amount of the bone differentiation promoter and bone formation promoter, in terms of solid content, for example, 0.00001% by mass or more, 0.0001% by mass or more, 0.001% by mass or more, 0.01% by mass or more, 0.1% by mass or more, 1% by mass or more, 3% by mass or more, 3.5% by mass or more, 5% by mass or more, 7% by mass or more, 10% by mass or more, 15% by mass or more, 20% by mass or more, 25% by mass or more, 30% by mass or more, 35% by mass or more, 40% by mass or more, 45% by mass or more, 50% by mass or more, 55% by mass or more, 60% by mass or more, 65% by mass or more, 70% by mass or more, 75% by mass or more, 80% by mass or more, 85% by mass or more, 90% by mass or more, 93% by mass or more, 95% by mass or more, 98% by mass or more, 99% by mass or more, or 100% by mass. The content of the above-mentioned active ingredient in the bone differentiation promoter and bone formation promoter is, based on the total amount of the bone differentiation promoter and bone formation promoter, in terms of solid content, for example, 100% by mass or less, 99% by mass or less, 98% by mass or less, 95% by mass or less, 93% by mass or less, 90% by mass or less, 85% by mass or less, 80% by mass or less, 75% by mass or less, 70% by mass or less, 65% by mass or less, 60% by mass or less, 55% by mass or less, 50% by mass or less, 45% by mass or less, 40% by mass or less, 35% by mass or less, 30% by mass or less, 25% by mass or less, 20% by mass or less, 15% by mass or less, 10% by mass or less, 8% by mass or less, 5% by mass or less, 3% by mass or less, or 1% by mass or less.

[0037] In the above-mentioned content of the bone differentiation promoter and bone formation promoter of the present invention, when two or more are selected from the group consisting of sebacic acid and its salts as active ingredients, the content of each component may be appropriately adjusted.

[0038] The bone differentiation promoter and bone formation promoter of the present invention can also be administered to humans, for example, for use in promoting bone differentiation and bone formation in the body. The bone differentiation promoter and bone formation promoter of the present invention may be administered orally, and oral administration includes enteral administration.

[0039] The dosage when the bone differentiation promoter and bone formation promoter of the present invention are administered orally may vary depending on the active ingredient, the form of the composition, and the method of application and dosage. For example, when it is sebacic acid or its salt, the dosage may be 0.1 mg to 20 mg of sebacic acid or its salt per day for an adult weighing 60 kg, preferably 0.5 mg to 15 mg of sebacic acid or its salt. The dosage can be appropriately increased or decreased according to factors such as the health status of the person taking it, the method of administration, the type of active ingredient, and the combination with other agents.

[0040] The bone differentiation promoter and bone formation promoter of the present invention may be administered once a day or divided into multiple times, such as twice a day or three times a day, as long as the effective dosage per day is within the above-mentioned range. The bone differentiation promoter and bone formation promoter of the present invention can obtain an effect immediately after administration, but continuous administration for 1 to 4 weeks or 1 month or more, 6 months or more, 1 year or more is preferable because the effect can be more sustained.

[0041] The bone differentiation promoter and bone formation promoter of the present invention can be used as foods and drinks (especially foods and drinks for the purpose of health care, health maintenance, promotion, etc. (for example, health foods, functional foods, nutritional compositions, dietary supplements, supplements, health foods, foods for specified health uses, foods with nutritional functions, or foods with functional claims)), quasi-drugs, pharmaceuticals, etc. In addition, the bone differentiation promoter and bone formation promoter of the present invention also include the meaning of additives that impart the effects of promoting bone differentiation and bone formation.

[0042] Foods, drinks, quasi-drugs, or pharmaceuticals containing sebacic acid or a salt thereof according to the present invention can be produced, for example, by adding sebacic acid or a salt thereof to intermediate products in the manufacturing processes of these products.

[0043] Sebacic acid or a salt thereof can be used as it is in the above foods and drinks, and if necessary, minerals, vitamins, flavonoids, quinones, polyphenols, amino acids, nucleic acids, essential fatty acids, cooling agents, binders, sweeteners, disintegrants, lubricants, coloring agents, flavors, stabilizers, gelling agents, preservatives, sustained-release regulators, surfactants, solvents, wetting agents, etc. can also be blended.

[0044] The foods and drinks include all foods and drinks that animals (including humans) can ingest. The types of foods and drinks are not particularly limited, and examples include dairy products; fermented foods (such as yogurt); beverages (soft drinks such as coffee, juice, and tea beverages, milk beverages, lactic acid bacteria beverages, beverages containing lactic acid bacteria, yogurt beverages, carbonated beverages, Japanese sake, Western liquor, fruit liquor, etc.); spreads (such as custard cream); pastes (such as fruit paste); Western confectionery (chocolate, doughnuts, pies, cream puffs, gums, gummies, jelly, candies, cookies, cakes, puddings, etc.); Japanese confectionery (dango, mochi, steamed buns, castella, anmitsu, yokan, etc.); frozen confectionery (ice cream, ice candy, sherbet, etc.); foods (curry, beef bowl, miso soup, soup, meat sauce, pasta, pickles, jam, etc.); seasonings (dressings, furikake, umami seasonings, soup bases, etc.).

[0045] The manufacturing method of the foods and drinks is not particularly limited, and can be appropriately carried out according to known methods.

[0046] The dosage unit form when used as a supplement is not particularly limited and can be appropriately selected, and examples include tablets such as chewables and troches, capsules, granules, liquids, powders, syrups, pastes, drinks, gummies, etc.

[0047] For the above-mentioned pharmaceutical, sebacic acid or its salt alone can be used, or it can be used in combination with other pharmaceutical ingredients described in the Japanese Pharmacopoeia, such as vitamins and crude drugs.

[0048] When preparing the bone differentiation promoter and bone formation promoter of the present invention as a pharmaceutical, sebacic acid or its salt is used together with ingredients acceptable in pharmaceuticals, in the form of tablets (including plain tablets, sugar-coated tablets, effervescent tablets, film-coated tablets, chewable tablets, troches, etc.), capsules, pills, powders (powders), fine granules, granules, liquids, suspensions, emulsions, syrups, pastes, injections (including the case of formulating with distilled water or an infusion such as an amino acid infusion or an electrolyte infusion as a liquid at the time of use), etc., and can be made into pharmaceutical preparations.

[0049] The administration of the pharmaceutical may be local or systemic. There is no particular limitation on the administration method, and it is administered orally or parenterally. Examples of parenteral administration routes include subcutaneous, intradermal, intramuscular, intraperitoneal, intravenous or intraarterial administration.

[0050] In addition to sebacic acid or its salt, the pharmaceutical of the present invention may optionally contain pharmaceutically acceptable ingredients such as excipients, binders, disintegrants, lubricants, coloring agents, suspending agents, thickening agents, antioxidants, absorption promoters, pH adjusters, preservatives, antiseptics, stabilizers, surfactants, sweeteners, flavoring agents, fragrances, etc.

[0051] Note that the pharmaceutical of the present invention also includes quasi-drugs.

[0052] The bone differentiation promoter and bone formation promoter of the present invention described above are applicable to mammals including humans (preferably humans).

[0053] Sebacic acid or a salt thereof contained as an active ingredient in the bone differentiation promoter and bone formation promoter of the present invention has a bone differentiation promoting action as shown in the examples described later, and thus is useful as an active ingredient of the bone differentiation promoter and bone formation promoter. In particular, sebacic acid or a salt thereof may have an action of activating the expression of Runx2 dependent on the Wnt / β-catenin signaling pathway in mesenchymal stem cells in the bone marrow, as also shown in the examples described later. Examples of the action based on the bone formation promoting action include a preventive action against osteoporosis (Int. J. Mol. Sci. 2018, 19, 360), and examples of the action based on the preventive action against osteoporosis include a preventive action against locomotive syndrome (locomotor organ syndrome). Therefore, sebacic acid or a salt thereof can also be used as an active ingredient of an osteoporosis preventive agent and a locomotive syndrome preventive agent. The above description regarding the bone differentiation promoter and bone formation promoter can be applied to the osteoporosis preventive agent and locomotive syndrome preventive agent. That is, the content, dosage, etc. of sebacic acid or a salt thereof in the osteoporosis preventive agent and locomotive syndrome preventive agent of the present invention are the same as above.

[0054] The osteoporosis preventive agent and locomotive syndrome preventive agent of the present invention can be used as foods and drinks (particularly, foods and drinks for the purpose of health care, health maintenance, promotion, etc. (for example, health foods, functional foods, nutritional compositions, dietary supplements, supplements, health foods, foods for specified health use, foods with nutritional functions, or foods with functional claims)), quasi-drugs, pharmaceuticals, etc. Further, the osteoporosis preventive agent and locomotive syndrome preventive agent of the present invention also include the meaning of additives that impart an osteoporosis preventive action and a locomotive syndrome preventive action. Foods and drinks, quasi-drugs, and pharmaceuticals are the same as those described above.

[0055] In addition, the bone differentiation promoter, bone formation promoter, osteoporosis preventive agent, and locomotive syndrome preventive agent of the present invention are highly safe because they contain natural-derived ingredients as active ingredients.

Examples

[0056] Hereinafter, the present invention will be described more specifically based on examples. However, the present invention is not limited to the following examples.

[0057] <Experimental method> The effect of promoting bone differentiation by sebacic acid (Sigma-Aldrich Co., LLC.) was verified according to the following method.

[0058] The bone marrow-derived mesenchymal stem cell line ST-2 (RIKEN BioResource Center) was seeded in a 12-well plate at a density of 1.0x10 5 cells / well. After one night, the cells were induced to differentiate for up to 14 days in a differentiation medium containing L-glutamine (2 mM), MEMα containing phenol red, antibiotics (penicillin-streptomycin), β-glycerophosphate (10 mM), ascorbic acid (50 μg / ml), and sebacic acid (10, 25 μM). The induction of bone differentiation was evaluated using alkaline phosphatase (ALP) staining and alizarin red staining.

[0059] For alkaline phosphatase staining, SIGMAFAST TM BCIP / NBT Tablet (Sigma-Aldrich, Cat: B5655-5TAB) was used to stain the differentiated cultured cells fixed with 70% ethanol, and imaging and quantitative analysis were performed using a BZ-X800 (KEYENCE CORPORATION).

[0060] For alizarin red staining, alizarin red S (Sigma-Aldrich, Cat: A5533) (40 mM) was added to the differentiated cultured cells, and the cells were stained for 20 minutes at room temperature with gentle shaking. Then, the alizarin red staining solution was removed, and the cells were washed with purified water. Imaging and quantitative analysis were performed using a BZ-X800 (KEYENCE CORPORATION).

[0061] Total proteins for protein quantification were extracted from cells recovered with lysis buffer containing phosphatase (Roche, Cat: 11097075001) supplemented with protease inhibitor cocktail (Cell signaling Technology, Cat: 5871), and the precipitate obtained by centrifugation at 4°C and 14,000 x g for 10 minutes was used. Western blotting was used to detect the target proteins. Rabbit anti-beta-catenin (Cell Signaling Technology, Cat: 9562S), Rabbit anti-Runx2 (Cell Signaling Technology, Cat: 12556), Mouse anti-beta-Actin (MBL, Cat: M177-3) were used as primary antibodies, and Goat Anti-Rabbit HRP (Jackson ImmunoResearch, Cat: 111-035-144), Goat Anti-Mouse HRP (Jackson ImmunoResearch, Cat: 115-035-146) were used as secondary antibodies. Images were taken using a LAS-4000 Imaging System (Fujifilm). ImageJ was used for quantitative analysis.

[0062] All results are shown as mean ± standard deviation (n = 3). The staining of ALP and alizarin red staining, and the expression levels of each protein were compared and evaluated against the Control group using ANOVA with post hoc test. The significance level was set at less than 5%.

[0063] <Experimental Results> The results of ALP staining 6 days after the start of differentiation induction are shown in Figure 1, the results of alizarin red staining 14 days after the start of differentiation induction are shown in Figure 2, and the results of protein expression of various osteogenic differentiation markers 3 days after the start of differentiation induction are shown in Figure 3.

[0064] Under the conditions of osteogenic differentiation induction, the addition of sebacic acid promoted the staining property indicating the activation of ALP (Figs. 1A and 1B) and the staining property of alizarin red staining reflecting the calcification ability by staining calcium deposited in osteogenically differentiated cells (Figs. 2A and 2B). Also, the protein amounts of β-catenin and Runx2 were increased by the addition of sebacic acid (Figs. 3A - 3C).

Claims

1. An osteogenic promoter containing sebacic acid or a salt thereof.

2. The osteogenic promoter according to claim 1, which has an activating effect on the expression of Runx2 dependent on the Wnt / β-catenin signaling pathway in mesenchymal stem cells in the bone marrow.

3. An osteogenesis promoter containing sebacic acid or a salt thereof.

4. An osteoporosis preventive agent containing the osteogenesis promoter according to claim 3.

5. A locomotive syndrome preventive agent containing the osteoporosis preventive agent according to claim 4.

6. The agent according to any one of claims 1 to 5, which is a food or drink, a pharmaceutical product, or a quasi-drug.

Images