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 a bone differentiation promoter and a bone formation promoter.Furthermore, the present invention relates to an agent for preventing osteoporosis and an agent for preventing locomotive syndrome. [Background technology]

[0002] Bones are constantly being regenerated, maintaining dynamic homeostasis through a delicate balance between destruction and formation. This remodeling, known as bone remodeling, begins with a series of processes: osteoclasts resorb (destroy) old bone (resorption phase). Next, macrophages phagocytose the old osteoclasts, suppressing their function (reversal phase), and osteoblasts secrete bone matrix to fill the missing areas (formation phase). After bone is filled by osteoblasts through bone formation, bone formation ceases (quiescent phase). Thus, the balance between bone destruction and formation is strictly regulated by both osteoblasts, which are responsible for bone formation, and osteoclasts, which are responsible for bone resorption. Disruption of this balance causes abnormalities in bone tissue, leading to various bone diseases such as osteoporosis.

[0003] Currently, bisphosphonates and other drugs are used to treat osteoporosis. However, there are still issues that need to be resolved, such as safety and efficacy, and the development of new therapeutic drugs that can resolve these issues is required. In particular, from the perspective of daily use, materials that can be used in both food and pharmaceuticals are desirable.

[0004] Royal jelly is a milky substance synthesized in the salivary glands of honeybees and secreted from the Mandebraan glands in their heads. It is given by worker bees to larvae placed in queen bee larvae cells in order to produce queen bees. Royal jelly is currently widely used around the world in health foods, medicines, cosmetics, and more, and its reported effects include increasing blood flow, lowering blood pressure, promoting growth, acting like a sex hormone, antibacterial, antitumor, promoting wound healing, curing autonomic nervous system disorders, anti-stress, promoting calcium absorption, lowering blood sugar levels, and antioxidant properties.

[0005] Non-patent document 1 reports that in a clinical trial involving 72 postmenopausal women, royal jelly intake alleviated the decrease in bone mineral density and the decrease in expression of bone formation markers seen in the placebo group.

[0006] Non-patent document 2 reports that the intake of royal jelly in menopausal model mice inhibited the decrease in bone density, and that the addition of royal jelly and 10-hydroxy-2-decenoic acid to mouse-derived bone marrow cells containing mesenchymal stem cells under conditions for inducing osteoclast differentiation inhibited the differentiation into osteoclasts.

[0007] Patent Document 1 reports 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 can be used as active ingredients in osteoporosis prevention agents. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] Japanese Patent Application Laid-Open No. 2006-62986 [Non-patent literature]

[0009] [Non-Patent Document 1] Climacteric,DOI:10.1080 / 13697137.2020.1806815 [Non-patent document 2] J.Biol.Chem.294(34)12224-12232(2020) Summary of the Invention [Problem to be solved by the invention]

[0010] However, neither Non-Patent Documents 1 and 2 nor Patent Document 1 confirms nor reports the bone differentiation promoting effect of sebacic acid.

[0011] An object of the present invention is to provide a novel agent for promoting bone differentiation and bone formation, as well as an agent for preventing osteoporosis and locomotive syndrome. [Means for solving the problem]

[0012] The present inventors have conducted extensive research to achieve the above-mentioned object and have found that sebacic acid, a metabolite of decanoic acid contained in royal jelly, has the effect of promoting bone differentiation via bone marrow-derived mesenchymal stem cells, thereby completing 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 its salt. [2] The bone differentiation promoter according to [1], which has the effect of activating Runx2 expression dependent on the Wnt / β-catenin signaling pathway in mesenchymal stem cells in bone marrow. [3] A bone formation promoter containing sebacic acid or a salt thereof. [4] An osteoporosis prevention agent comprising the bone formation promoter described in [3]. [5] A prophylactic agent for locomotive syndrome, comprising the prophylactic agent for osteoporosis according to [4]. [6] The agent according to any one of [1] to [5], which is a food or drink, a medicine, or a quasi-drug. [Effects of the Invention]

[0014] Sebacic acid contained in royal jelly has the effect of promoting bone differentiation, and is therefore useful as an active ingredient in bone differentiation promoters, bone formation promoters, osteoporosis preventive agents, and locomotive syndrome preventive agents. [Brief explanation of the drawings]

[0015] [Figure 1]Graphs showing (A) an ALP staining image and (B) quantification results of ST2 cells 6 days after the start of differentiation induction. *P<0.05, **P<0.01 [Figure 2] Graphs showing (A) an image of alizarin red staining of ST2 cells 14 days after the start of differentiation induction and (B) the quantification results. ****P<0.0001 [Figure 3] Photographs and graphs showing the protein expression of various bone differentiation markers in ST2 cells 3 days after the start of differentiation induction. (A) Western blotting results, (B) graph showing the quantification results of β-catenin, (C) graph showing the quantification results of Runx2, *P<0.05, ***P<0.001 DETAILED DESCRIPTION OF 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, the term "comprise" encompasses the meanings of "essentially consist of" and "consist of only."

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

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

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

[0021] [ka]

[0022] Sebacic acid is a fatty acid found in royal jelly. It is metabolized in the body from 10-hydroxydecanoic acid, which is also a fatty acid found in royal jelly. Sebacic acid or its salts may be synthetic or naturally derived, for example, from royal jelly. Royal jelly-derived sebacic acid can be obtained, for example, by extraction and purification from royal jelly using an organic solvent. After synthesis or extraction, sebacic acid or its salts can be purified using methods commonly used by those skilled in the art. Purification methods are not particularly limited, and examples include precipitation, liquid-liquid countercurrent distribution, adsorption treatment with activated carbon or resin, column chromatography, ion exchange chromatography, and the like. It is not necessary to isolate and purify sebacic acid or its salts to a purity of 100% by mass. The sebacic acid or salt thereof used in the present invention may generally have a purity of 50% by mass or more, preferably 80% by mass or more, and more preferably 90% by mass or more.

[0023] In the present invention, sebacic acid or a salt thereof can be used in either an unisolated or unpurified state (crude extract) or an isolated or purified state.

[0024] The salt of sebacic acid is 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; tetramethylammonium salt, tetraethylammonium salt, benzyltrimethylammonium salt, quaternary ammonium salts such as arginine salt, lysine salt, histidine salt, arginine salt, aspartate, glutamate, etc.; inorganic acid salts such as hydrochloride, sulfate, nitrate, phosphate, carbonate, bicarbonate, perchlorate, etc.; organic acid salts such as acetate, propionate, lactate, maleate, fumarate, tartrate, malate, citrate, ascorbate, etc.; sulfonate salts such as methanesulfonate, isethionate, benzenesulfonate, p-toluenesulfonate, etc.

[0025] Royal jelly is a milky white jelly-like substance produced by mixing secretions from the hypopharyngeal and mandibular glands of 3- to 12-day-old worker honeybees. Royal jelly in the present invention includes raw royal jelly, dried royal jelly, dried royal jelly powder, enzyme-treated royal jelly, royal jelly extract, and royal jelly fermentation product. Royal jelly may be produced in any of Europe, Oceania, America, Brazil, Japan, China, other Asian countries, etc.

[0026] Dried royal jelly powder is made by drying and powdering fresh royal jelly.

[0027] As the drying method, any known method employed in general food processing can be used, such as natural drying such as ventilation drying or sun drying, forced drying in which heating is performed using electricity or the like, freeze drying, etc. Freeze drying is preferred.

[0028] Enzyme-treated royal jelly is royal jelly treated with a protease. The royal jelly used to produce the enzyme-treated royal jelly is not particularly limited, and examples thereof include raw royal jelly, royal jelly powder obtained by drying and powdering raw royal jelly, and raw royal jelly extracted with water or aqueous ethanol.

[0029] Enzyme-treated royal jelly can be produced by treating royal jelly raw materials with an enzyme having at least endopeptidase activity, an enzyme having at least exopeptidase activity, and / or an enzyme having both endopeptidase activity and exopeptidase activity.

[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, Rhizopus, etc.), and pancreatin and pepsin, which also have endopeptidase activity.

[0032] Among these 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 name: Protease A, Flavorzyme, Proteax), and peptidase produced by Aspergillus melleus (trade name: Protease P). Preferred examples of enzymes having exoprotease activity include peptidase produced by Aspergillus oryzae (trade name: Umamizyme G, Promod 192P, Promod 194P, Sumizyme FLAP), and peptidase produced by Aspergillus sojae (trade name: Sternzyme B15024), peptidase produced by the genus Aspergillus (trade name: Coclase P), and peptidase produced by Rhizopus oryzae (trade name: Peptidase R). Further preferred examples of enzymes having endoprotease activity include peptidases produced by Bacillus subtilis (trade names: Orientase 22BF, Nucleicin), peptidases produced by Bacillus licheniformis (trade name: Alcalase), peptidases produced by Bacillus stearothermophilus (trade name: Protease S), peptidases produced by Bacillus amyloliquefaciens (trade name: Neutrase), and peptidases produced by the genus Bacillus (trade name: Protamex).

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

[0034] The royal jelly fermented product 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 solely of sebacic acid or a salt thereof, or may contain only sebacic acid or a salt thereof as the active ingredient. Furthermore, the bone differentiation promoter and bone formation promoter of the present invention may contain other ingredients as long as the bone differentiation promoting effect 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 of the present invention may be, for example, 0.00001% by mass or more, 0.0001% 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, or more, in terms of solid content relative to the total amount of the bone differentiation promoter and bone formation promoter. % or more, 20 mass% or more, 25 mass% or more, 30 mass% or more, 35 mass% or more, 40 mass% or more, 45 mass% or more, 50 mass% or more, 55 mass% or more, 60 mass% or more, 65 mass% or more, 7 It may be 0% 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, in terms of solid content relative to the total amount of the bone differentiation promoter and bone formation promoter, may be, 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] When two or more active ingredients are selected from the group consisting of sebacic acid and salts thereof, the above-mentioned content of each ingredient in the bone differentiation promoter and bone formation promoter of the present invention may be adjusted appropriately.

[0038] The bone differentiation promoter and bone formation promoter of the present invention can 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 of the bone differentiation promoter and bone formation promoter of the present invention when administered orally may vary depending on the active ingredient, the form of the composition, and the application method and amount, but for example, in the case of sebacic acid or a salt thereof, the dosage for an adult weighing 60 kg may be 0.1 mg to 20 mg of sebacic acid or a salt thereof, preferably 0.5 mg to 15 mg of sebacic acid or a salt thereof, per day. This dosage can be increased or decreased as appropriate depending on factors such as the health condition 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 in divided doses such as twice or three times a day, as long as the effective daily dose is within the above-mentioned range. The bone differentiation promoter and bone formation promoter of the present invention exhibit their effects immediately after administration, but continuous administration for 1 to 4 weeks, or for one month or more, six months or more, or one year or more is preferred because the effects can be sustained longer.

[0041] The bone differentiation promoter and bone formation promoter of the present invention can be used as foods and beverages (particularly foods and beverages intended for health, health maintenance, or promotion (e.g., health foods, functional foods, nutritional compositions, dietary supplements, supplements, health foods, foods for specified health uses, foods with nutrient functions, or foods with functional claims)), quasi-drugs, pharmaceuticals, etc. The bone differentiation promoter and bone formation promoter of the present invention also encompass the meaning of additives that impart bone differentiation promoting action and bone formation promoting action.

[0042] The food and drink products, quasi-drugs, or pharmaceutical products containing sebacic acid or a salt thereof of the present invention as an ingredient can be produced, for example, by adding sebacic acid or a salt thereof to intermediate products in the production process of these products.

[0043] In the above-mentioned foods and beverages, sebacic acid or a salt thereof can be used as it is, and if necessary, minerals, vitamins, flavonoids, quinones, polyphenols, amino acids, nucleic acids, essential fatty acids, cooling agents, binders, sweeteners, disintegrants, lubricants, colorants, flavorings, stabilizers, gelling agents, preservatives, sustained-release regulators, surfactants, solubilizers, humectants, etc. can also be blended.

[0044] Food and beverage products include any food and beverage product that can be consumed by animals (including humans). The types of food and beverage products are not particularly limited, and examples include dairy products; fermented foods (yogurt, etc.); beverages (soft drinks such as coffee, juice, and tea drinks, dairy drinks, lactic acid bacteria drinks, drinks containing lactic acid bacteria, yogurt drinks, carbonated drinks, sake, Western liquor, and alcoholic beverages such as fruit wine); spreads (custard cream, etc.); pastes (fruit paste, etc.); Western confectionery products (chocolate, donuts, pies, cream puffs, gum, gummy candies, jellies, candies, cookies, cakes, puddings, etc.); Japanese confectionery products (daifuku, mochi, manju, castella, anmitsu, yokan, etc.); frozen desserts (ice cream, popsicles, sorbets, etc.); foods (curry, beef bowls, rice porridge, miso soup, soup, meat sauce, pasta, pickles, jam, etc.); and seasonings (dressings, furikake, umami seasonings, soup bases, etc.).

[0045] The method for producing the food or drink is not particularly limited, and any known method can be used as appropriate.

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

[0047] The above-mentioned pharmaceuticals may contain sebacic acid or its salts alone, or may be used in combination with other pharmaceutical ingredients listed in the Japanese Pharmacopoeia, such as vitamins and herbal medicines.

[0048] When the bone differentiation promoter and bone formation promoter of the present invention are prepared as pharmaceuticals, sebacic acid or a salt thereof can be prepared together with pharmaceutical acceptable ingredients into the form of tablets (including plain tablets, sugar-coated tablets, effervescent tablets, film-coated tablets, chewable tablets, troches, etc.), capsules, pills, powders (pulverized medicines), fine granules, granules, liquids, suspensions, emulsions, syrups, pastes, injections (including the case where the agent is mixed with distilled water or an infusion such as an amino acid infusion or an electrolyte infusion at the time of use to prepare a liquid), etc., to form a pharmaceutical preparation.

[0049] Pharmaceuticals may be administered locally or systemically. There are no particular limitations on the administration method, and they may be administered orally or parenterally. Parenteral administration routes include subcutaneous, intradermal, intramuscular, intraperitoneal, intravenous, and intraarterial administration.

[0050] In addition to sebacic acid or a salt thereof, the pharmaceutical of the present invention may contain, as needed, pharmaceutically acceptable ingredients such as excipients, binders, disintegrants, lubricants, colorants, suspending agents, thickeners, antioxidants, absorption enhancers, pH adjusters, preservatives, antiseptics, stabilizers, surfactants, sweeteners, flavoring agents, and fragrances.

[0051] The pharmaceuticals of the present invention also include 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] As shown in the examples below, sebacic acid or a salt thereof, contained as an active ingredient in the bone differentiation promoter and bone formation promoter of the present invention, exhibits bone differentiation promoting activity and is therefore useful as an active ingredient for bone differentiation promoters and bone formation promoters. In particular, as shown in the examples below, sebacic acid or a salt thereof can activate Runx2 expression in bone marrow mesenchymal stem cells in a Wnt / β-catenin signaling pathway-dependent manner. Examples of effects based on bone formation promoting activity include osteoporosis prevention ( Int. J. Mol. Sci. 2018, 19, 360 ), and examples of effects based on osteoporosis prevention include locomotive syndrome (musculoskeletal syndrome). Therefore, sebacic acid or a salt thereof can also be used as an active ingredient in osteoporosis prevention agents and locomotive syndrome prevention agents. The above descriptions regarding bone differentiation promoters and bone formation promoters can be applied to osteoporosis prevention agents and locomotive syndrome prevention agents. That is, the content, dosage, etc. of sebacic acid or a salt thereof in the agent for preventing osteoporosis and the agent for preventing locomotive syndrome of the present invention are the same as those described above.

[0054] The osteoporosis preventive agent and locomotive syndrome preventive agent of the present invention can be used as a food or drink (particularly a food or drink intended for health, health maintenance, or promotion, etc. (e.g., health food, functional food, nutritional composition, nutritional supplement, supplement, health food, food for specified health use, nutrient functional food, or food with functional claims)), quasi-drug, pharmaceutical, etc. The osteoporosis preventive agent and locomotive syndrome preventive agent of the present invention also encompasses the meaning of an additive that imparts an osteoporosis preventive effect and a locomotive syndrome preventive effect. The food or drink, quasi-drug, and pharmaceutical are the same as those described above.

[0055] Furthermore, 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 naturally occurring components as active ingredients. [Example]

[0056] The present invention will be described in more detail below with reference to examples, although the present invention is not limited to the following examples.

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

[0058] Bone marrow-derived mesenchymal stem cell line ST-2 (RIKEN BioResource Research Center) was added to a 12-well plate at 1.0 x 10 5 After overnight incubation, cells were induced to differentiate for up to 14 days in differentiation medium containing MEMα containing L-glutamine (2 mM) and phenol red, antibiotics (penicillin and streptomycin), β-glycerophosphate (10 mM), ascorbic acid (50 μg / ml), and sebacic acid (10.25 μM). Osteogenesis was assessed by alkaline phosphatase (ALP) staining and Alizarin Red staining.

[0059] Alkaline phosphatase staining was performed on cultured cells after differentiation induction fixed with 70% ethanol. TM The tissue was stained using BCIP / NBT Tablet (Sigma-Aldrich, Cat: B5655-5TAB), and images were taken and quantitative analysis was performed using a BZ-X800 (Keyence Corporation).

[0060] Alizarin red staining was performed by adding Alizarin Red S (Sigma-Aldrich, Cat: A5533) (40 mM) to the cultured cells after differentiation induction and staining with gentle shaking at room temperature for 20 minutes. The Alizarin Red staining solution was then removed and the cells were washed with purified water. Photography and quantitative analysis were performed using a BZ-X800 (Keyence Corporation).

[0061] Total protein for protein quantification was extracted from harvested cells using phosphatase-containing lysis buffer (Roche, Cat: 11097075001) supplemented with a protease inhibitor cocktail (Cell signaling Technology, Cat: 5871), and the precipitate was centrifuged at 14,000 × g for 10 minutes at 4°C. Western blotting was performed to detect target proteins. Primary antibodies were rabbit anti-beta-catenin (Cell Signaling Technology, Cat. No. 9562S), rabbit anti-Runx2 (Cell Signaling Technology, Cat. No. 12556), and mouse anti-beta-actin (MBL, Cat. No. M177-3). Secondary antibodies were goat anti-rabbit HRP (Jackson ImmunoResearch, Cat. No. 111-035-144) and goat anti-mouse HRP (Jackson ImmunoResearch, Cat. No. 115-035-146). Images were captured using an LAS-4000 Imaging System (Fujifilm). Quantitative analysis was performed using ImageJ.

[0062] All results are shown as mean ± standard deviation (n = 3). ALP staining, Alizarin Red staining, and protein expression levels were evaluated using ANOVA with post hoc tests, comparing the results with those of the control group. 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 bone differentiation markers 3 days after the start of differentiation induction are shown in Figure 3.

[0064] Under osteogenic differentiation conditions, the addition of sebacic acid promoted the staining of ALP (Fig. 1A, B) and alizarin red (Fig. 2A, B), which stains calcium deposited in osteogenic differentiated cells and reflects mineralization potential. Furthermore, the addition of sebacic acid also increased the protein levels of β-catenin and Runx2 (Fig. 3A-C).

Claims

1. A bone differentiation promoter for bone marrow-derived mesenchymal stem cells, comprising sebacic acid or a salt thereof.

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

3. An activator of Wnt / β-catenin signaling pathway-dependent Runx2 expression in mesenchymal stem cells in bone marrow, comprising sebacic acid or a salt thereof.

4. The agent according to any one of claims 1 to 3, which is a food or drink, a medicine, or a quasi-drug.

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