The role of small molecules in bone regeneration

Future Medicinal Chemistry

Volumn 5, Issue 14, 2013, Pages 1671-1684

  Han, Qian Qian ^a   Du, Yi ^b   Yang, Pi Shan ^a  

^a SHANDONG UNIVERSITY   (China)

^b JINAN STOMATOLOGICAL HOSPITAL   (China)

Author keywords

[No Author keywords available]

Indexed keywords

1,3,8 TRIHYDROXY 2 METHOXY ANTHRAQUINONE; 2 HYDROXY 1 METHOXY ANTHRAQUINONE; 3,3',4',5,7 PENTAHYDROXYFLAVONE 6 C BETA DEXTRO GLUCOPYRANOSIDE; 6 C BETA DEXTRO GLUCOPYRANOSYL 3',4',5,7 TETRAHYDROXYFLAVANOL; AURANTIIN; CATHEPSIN K INHIBITOR; DAIDZEIN; DECALPENIC ACID; FLAVONOID; GLYCOGEN SYNTHASE KINASE 3 INHIBITOR; HESPERIDIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; KAEMPFEROL; L 006235; NERVE GROWTH FACTOR; ODANACATIB; ONO 5334; PHYTOESTROGEN; PLACEBO; PLANT EXTRACT; PONCIRIN; PYRAZOLONE DERIVATIVE; QUERCETIN DERIVATIVE; QUINONE DERIVATIVE; RECOMBINANT BONE MORPHOGENETIC PROTEIN 2; RETINOIC ACID; RUBIADIN; THYMOQUINONE; UNCLASSIFIED DRUG; UNINDEXED DRUG; WNT PROTEIN;

ALLOGRAFT; AUTOGRAFT; BONE DEFECT; BONE DENSITY; BONE DISEASE; BONE GRAFT; BONE METABOLISM; BONE MINERAL; BONE REGENERATION; CELL DIFFERENTIATION; CHEMICAL STRUCTURE; CHINESE MEDICINE; CORTICOSTEROID INDUCED OSTEOPOROSIS; DIABETES MELLITUS; DRUG SAFETY; DRUG SCREENING; DRUG TARGETING; ENZYME ACTIVATION; ENZYME INHIBITION; GENETIC TRANSCRIPTION; HUMAN; LUMBAR SPINE; NONHUMAN; OSTEOBLAST; OSTEOCLAST; OSTEOLYSIS; OSTEOPENIA; OSTEOPOROSIS; PENICILLIUM; PENICILLIUM VERRUCULOSUM; PHASE 3 CLINICAL TRIAL (TOPIC); POSTMENOPAUSE OSTEOPOROSIS; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; REGENERATIVE MEDICINE; REVIEW; SIGNAL TRANSDUCTION; SPINE FUSION; TISSUE ENGINEERING; TRADITIONAL MEDICINE; TREATMENT OUTCOME; VERTEBRA BODY;

ANIMALS; BONE AND BONES; BONE REGENERATION; DRUG DISCOVERY; HUMANS; SMALL MOLECULE LIBRARIES;

EID: 84884583510     PISSN: 17568919     EISSN: 17568927     Source Type: Journal    
DOI: 10.4155/fmc.13.133     Document Type: Review

References (99)

1. Ontoria JM, Altamura S, Di Marco A et al. Identification of novel, selective, and stable inhibitors of class II histone deacetylases. Validation studies of the inhibition of the enzymatic activity of HDAC4 by small molecules as a novel approach for cancer therapy. J. Med. Chem. 52(21), 6782-6789 (2009).
2. Banaszynski LA, Chen LC, Maynard-Smith LA, Ooi AG, Wandless TJ. A rapid, reversible, and tunable method to regulate protein function in living cells using synthetic small molecules. Cell 126(5), 995-1004 (2006).
3. Sommerfeldt DW, Rubin CT. Biology of bone and how it orchestrates the form and function of the skeleton. Eur. Spine J. 10(Suppl. 2), S86-S95 (2001).
4. Amini AR, Laurencin CT, Nukavarapu SP. Bone tissue engineering: Recent advances and challenges. Crit. Rev. Biomed. Eng. 40(5), 363-408 (2012).
5. Giannoudis PV, Dinopoulos H, Tsiridis E. Bone substitutes: An update. Injury 36(Suppl 3), S20-S27 (2005).
6. Eppley BL, Pietrzak WS, Blanton MW. Allograft and alloplastic bone substitutes: A review of science and technology for the craniomaxillofacial surgeon. J. Craniofac. Surg. 16(6), 981-989 (2005).
7. Boyce T, Edwards J, Scarborough N. Allograft bone. The influence of processing on safety and performance. Orthop. Clin. North Am. 30(4), 571-581 (1999).
8. Hamadouche M, Karoubi M, Dumaine V, Courpied JP. The use of fibre-based demineralised bone matrix in major acetabular reconstruction: Surgical technique and preliminary results. Int. Orthop. 35(2), 283-288 (2011).
9. Thitiset T, Damrongsakkul S, Bunaprasert T, Leeanansaksiri W, Honsawek S. Development of collagen/demineralized bone powder scaffolds and periosteum-derived cells for bone tissue engineering application. Int. J. Mol. Sci. 14(1), 2056-2071 (2013).
10. Kaigler D, Cirelli JA, Giannobile WV. Growth factor delivery for oral and periodontal tissue engineering. Exp. Opin. Drug Deliv. 3(5), 647-662 (2006).
11. Sun P, Wang J, Zheng Y, Fan Y, Gu Z. BMP2/7 heterodimer is a stronger inducer of bone regeneration in peri-implant bone defects model than BMP2 or BMP7 homodimer. Dent. Mater. J. 31(2), 239-248 (2012).
12. Rosen V. BMP2 signaling in bone development and repair. Cytokine Growth Factor Rev. 20(5-6), 475-480 (2009).
13. Xiao C, Zhou H, Liu G et al. Bone marrow stromal cells with a combined expression of BMP-2 and VEGF-165 enhanced bone regeneration. Biomed. Mater. 6(1), 015013 (2011).
14. Yan XZ, Ge SH, Sun QF, Guo HM, Yang PS. A pilot study evaluating the effect of recombinant human bone morphogenetic protein-2 and recombinant human beta-nerve growth factor on the healing of Class III furcation defects in dogs. J. Periodontol. 81(9), 1289-1298 (2010).
15. Thamm DH, Kurzman ID, Clark MA et al. Preclinical investigation of PEGylated tumor necrosis factor alpha in dogs with spontaneous tumors: Phase I evaluation. Clin. Cancer Res. 16(5), 1498-1508 (2010).
16. Olabisi RM, Lazard Z, Heggeness MH et al. An injectable method for noninvasive spine fusion. Spine J. 11(6), 545-556 (2011).
17. Lewandrowski KU, Nanson C, Calderon R. Vertebral osteolysis after posterior interbody lumbar fusion with recombinant human bone morphogenetic protein 2: A report of five cases. Spine J. 7(5), 609-614 (2007).
18. McClellan JW, Mulconrey DS, Forbes RJ, Fullmer N. Vertebral bone resorption after transforaminal lumbar interbody fusion with bone morphogenetic protein (rhBMP-2). J. Spinal Disord. Tech. 19(7), 483-486 (2006).
19. Jaiswal R, Deo V. Evaluation of the effectiveness of enamel matrix derivative, bone grafts, and membrane in the treatment of mandibular Class II furcation defects. Int. J. Periodontics Restorative Dent. 33(2), e58-e64 (2013).
20. Nevins M, Kao RT, McGuire MK et al. Platelet-derived growth factor promotes periodontal regeneration in localized osseous defects: 36-month extension results from a randomized, controlled, double-masked clinical trial. J. Periodontol. 84(4), 456-464 (2013).
21. Spring DR. Chemical genetics to chemical genomics: Small molecules offer big insights. Chem. Soc. Rev. 34(6), 472-482 (2005).
22. Iljin K, Ketola K, Vainio P et al. High-throughput cell-based screening of 4910 known drugs and drug-like small molecules identifies disulfiram as an inhibitor of prostate cancer cell growth. Clin. Cancer Res. 15(19), 6070-6078 (2009).
23. Lyssiotis CA, Lairson LL, Boitano AE, Wurdak H, Zhu S, Schultz PG. Chemical control of stem cell fate and developmental potential. Angew. Chem. Int. Ed. Engl. 50(1), 200-242 (2011).
24. Liu L, Suzuki K, Nakagata N et al. Retinoic acid signaling regulates Sonic hedgehog and bone morphogenetic protein signalings during genital tubercle development. Birth Defects Res. B Dev. Reprod. Toxicol. 95(1), 79-88 (2011).
25. Sheng N, Xie Z, Wang C et al. Retinoic acid regulates bone morphogenic protein signal duration by promoting the degradation of phosphorylated Smad1. Proc. Natl Acad. Sci. USA 107(44), 18886-18891 (2010).
26. Sakamoto S, Kojima F, Momose I, Kawada M, Adachi H, Nishimura Y. Decalpenic acid induces early osteoblastic markers in pluripotent mesenchymal cells via activation of retinoic acid receptor gamma. Biochem. Biophys. Res. Commun. 422(4), 751-757 (2012).
27. Wattel A, Kamel S, Mentaverri R et al. Potent inhibitory effect of naturally occurring flavonoids quercetin and kaempferol on in vitro osteoclastic bone resorption. Biochem. Pharmacol. 65(1), 35-42 (2003).
28. Kim YJ, Bae YC, Suh KT, Jung JS. Quercetin, a flavonoid, inhibits proliferation and increases osteogenic differentiation in human adipose stromal cells. Biochem. Pharmacol. 72(10), 1268-1278 (2006).
29. Yamaguchi M, Weitzmann MN. Quercetin, a potent suppressor of NF-kB and Smad activation in osteoblasts. Int. J. Mol. Med. 28(4), 521-525 (2011).
30. Derakhshanian H, Ghadbeigi S, Rezaian M et al. Quercetin improves bone strength in experimental biliary cirrhosis. Hepatol. Res. 43(4), 394-400 (2013).
31. Liang W, Luo Z, Ge S et al. Oral administration of quercetin inhibits bone loss in rat model of diabetic osteopenia. Eur. J. Pharmacol. 670(1), 317-324 (2011).
32. Siddiqui JA, Swarnkar G, Sharan K et al. A naturally occurring rare analog of quercetin promotes peak bone mass achievement and exerts anabolic effect on osteoporotic bone. Osteoporos. Int. 22(12), 3013-3027 (2011).
33. Sharan K, Mishra JS, Swarnkar G et al. A novel quercetin analogue from a medicinal plant promotes peak bone mass achievement and bone healing after injury and exerts an anabolic effect on osteoporotic bone: The role of aryl hydrocarbon receptor as a mediator of osteogenic action. J. Bone Miner. Res. 26(9), 2096-2111 (2011).
34. Zhang P, Dai KR, Yan SG et al. Effects of naringin on the proliferation and osteogenic differentiation of human bone mesenchymal stem cell. Eur. J. Pharmacol. 607(1-3), 1-5 (2009).
35. Pang WY, Wang XL, Mok SK et al. Naringin improves bone properties in ovariectomized mice and exerts oestrogen-like activities in rat osteoblast-like (UMR-106) cells. Br. J. Pharmacol. 159(8), 1693-1703 (2010).
36. Chen LL, Lei LH, Ding PH, Tang Q, Wu YM. Osteogenic effect of Drynariae rhizoma extracts and Naringin on MC3T3-E1 cells and an induced rat alveolar bone resorption model. Arch. Oral Biol. 56(12), 1655-1662 (2011).
37. Ang ES, Yang X, Chen H, Liu Q, Zheng MH, Xu J. Naringin abrogates osteoclastogenesis and bone resorption via the inhibition of RANKL-induced NF-kB and ERK activation. FEBS Lett. 585(17), 2755-2762 (2011).
38. Wong RW, Rabie AB. Effect of naringin collagen graft on bone formation. Biomaterials 27(9), 1824-1831 (2006).
39. Horcajada MN, Habauzit V, Trzeciakiewicz A et al. Hesperidin inhibits ovariectomized-induced osteopenia and shows differential effects on bone mass and strength in young and adult intact rats. J. Appl. Physiol. 104(3), 648-654 (2008).
40. Chiba H, Uehara M, Wu J et al. Hesperidin, a citrus flavonoid, inhibits bone loss and decreases serum and hepatic lipids in ovariectomized mice. J. Nutr. 133(6), 1892-1897 (2003).
41. Yoon HY, Yun SI, Kim BY et al. Poncirin promotes osteoblast differentiation but inhibits adipocyte differentiation in mesenchymal stem cells. Eur. J. Pharmacol. 664(1-3), 54-59 (2011).
42. Yoon HY, Won YY, Chung YS. Poncirin prevents bone loss in glucocorticoid-induced osteoporosis in vivo and in vitro. J. Bone Miner. Metab. 30(5), 509-516 (2012).
43. Bao L, Qin L, Liu L et al. Anthraquinone compounds from Morinda officinalis inhibit osteoclastic bone resorption in vitro. Chem. Biol. Interact. 194(2-3), 97-105 (2011).
44. Lee SU, Shin HK, Min YK, Kim SH. Emodin accelerates osteoblast differentiation through phosphatidylinositol 3-kinase activation and bone morphogenetic protein-2 gene expression. Int. Immunopharmacol. 8(5), 741-747 (2008).
45. Xiang MX, Xu Z, Su HW, Hu J, Yan YJ. Emodin-8-O-b-d-glucoside from polygonum amplexicaule D. Don var. sinense Forb. promotes proliferation and differentiation of osteoblastic MC3T3-E1 cells. Molecules 16(1), 728-737 (2011).
46. Sagai M, Bocci V. Mechanisms of action involved in ozone therapy: Is healing induced via a mild oxidative stress? Med. Gas Res. 1, 29 (2011).
47. Wirries A, Schubert AK, Zimmermann R, Jabari S, Ruchholtz S, El-Najjar N. Thymoquinone accelerates osteoblast differentiation and activates bone morphogenetic protein-2 and ERK pathway. Int. Immunopharmacol. 15(2), 381-386 (2013).
48. Salles JP, Laurencin-Dalicieux S, Conte-Auriol F, Briand-Mesange F, Gennero I. Bone defects in LPA receptor genetically modified mice. Biochim. Biophys. Acta 1831(1), 93-98 (2013).
49. Liu YB, Kharode Y, Bodine PV, Yaworsky PJ, Robinson JA, Billiard J. LPA induces osteoblast differentiation through interplay of two receptors: LPA1 and LPA4. J. Cell. Biochem. 109(4), 794-800 (2010).
50. Gennero I, Laurencin-Dalicieux S, Conte-Auriol F et al. Absence of the lysophosphatidic acid receptor LPA1 results in abnormal bone development and decreased bone mass. Bone 49(3), 395-403 (2011).
51. Mansell JP, Nowghani M, Pabbruwe M, Paterson IC, Smith AJ, Blom AW. Lysophosphatidic acid and calcitriol co-operate to promote human osteoblastogenesis: Requirement of albumin-bound LPA. Prostaglandins Other Lipid Mediat. 95(1-4), 45-52 (2011).
52. Ishii M, Egen JG, Klauschen F et al. Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis. Nature 458(7237), 524-528 (2009).
53. Ishii M, Kikuta J, Shimazu Y, Meier-Schellersheim M, Germain RN. Chemorepulsion by blood S1P regulates osteoclast precursor mobilization and bone remodeling in vivo. J. Exp. Med. 207(13), 2793-2798 (2010).
54. Moon RT. Wnt/beta-catenin pathway. Sci. STKE 2005(271), cm1 (2005).
55. Meijer L, Flajolet M, Greengard P. Pharmacological inhibitors of glycogen synthase kinase 3. Trends Pharmacol. Sci. 25(9), 471-480 (2004).
56. Jope RS, Johnson GV. The glamour and gloom of glycogen synthase kinase-3. Trends Biochem. Sci. 29(2), 95-102 (2004).
57. Die L, Yan P, Jun Jiang Z, Min Hua T, Cai W, Xing L. Glycogen synthase kinase-3 beta inhibitor suppresses Porphyromonas gingivalis lipopolysaccharide- induced CD40 expression by inhibiting nuclear factor-kappa B activation in mouse osteoblasts. Mol. Immunol. 52(1), 38-49 (2012).
58. Clement-Lacroix P, Ai M, Morvan F et al. Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice. Proc. Natl Acad. Sci. USA 102(48), 17406-17411 (2005).
59. Kulkarni NH, Onyia JE, Zeng Q et al. Orally bioavailable GSK-3alpha/beta dual inhibitor increases markers of cellular differentiation in vitro and bone mass in vivo. J. Bone Mineral Res. 21(6), 910-920 (2006).
60. Marsell R, Sisask G, Nilsson Y et al. GSK-3 inhibition by an orally active small molecule increases bone mass in rats. Bone 50(3), 619-627 (2012).
61. Bodine PV, Zhao W, Kharode YP et al. The Wnt antagonist secreted frizzled-related protein-1 is a negative regulator of trabecular bone formation in adult mice. Mol. Endocrinol. 18(5), 1222-1237 (2004).
62. Bodine PV, Stauffer B, Ponce-de-Leon H et al. A small molecule inhibitor of the Wnt antagonist secreted frizzled-related protein-1 stimulates bone formation. Bone 44(6), 1063-1068 (2009).
63. Chan A, van Bezooijen RL, Lowik CW. A new paradigm in the treatment of osteoporosis: Wnt pathway proteins and their antagonists. Curr. Opin. Investig. Drugs 8(4), 293-298 (2007).
64. Pelletier JC, Lundquist JT 4th, Gilbert AM et al. (1-(4-(naphthalen-2-yl) pyrimidin-2-yl)piperidin-4-yl)methanamine: A wingless beta-catenin agonist that increases bone formation rate. J. Med. Chem. 52(22), 6962-6965 (2009).
65. Palmer JT, Bryant C, Wang DX et al. Design and synthesis of tri-ring P3 benzamide-containing aminonitriles as potent, selective, orally effective inhibitors of cathepsin K. J. Med. Chem. 48(24), 7520-7534 (2005).
66. Ochi Y, Yamada H, Mori H et al. Effects of ONO-5334, a novel orally-active inhibitor of cathepsin K, on bone metabolism. Bone 49(6), 1351-1356 (2011).
67. Ng KW. Potential role of odanacatib in the treatment of osteoporosis. Clin. Interv. Aging 7, 235-247 (2012).
68. Bone HG, McClung MR, Roux C et al. Odanacatib, a cathepsin-K inhibitor for osteoporosis: A two-year study in postmenopausal women with low bone density. J. Bone Mineral Res. 25(5), 937-947 (2010).
69. Kwak HB, Kim HS, Lee MS et al. Pyridone 6, a pan-Janus-activated kinase inhibitor, suppresses osteoclast formation and bone resorption through down-regulation of receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL)-induced c-Fos and nuclear factor of activated T cells (NFAT) c1 expression. Biol. Pharm. Bull. 32(1), 45-50 (2009).
70. Kim MH, Ryu SY, Choi JS, Min YK, Kim SH. Saurolactam inhibits osteoclast differentiation and stimulates apoptosis of mature osteoclasts. J. Cell. Physiol. 221(3), 618-628 (2009).
71. Wang C, Steer JH, Joyce DA, Yip KH, Zheng MH, Xu J. 12-O- tetradecanoylphorbol-13-acetate (TPA) inhibits osteoclastogenesis by suppressing RANKL-induced NF-kappaB activation. J. Bone Mineral Res. 18(12), 2159-2168 (2003).
72. Lee JW, Iwahashi A, Hasegawa S et al. Coptisine inhibits RANKL-induced NF-kappaB phosphorylation in osteoclast precursors and suppresses function through the regulation of RANKL and OPG gene expression in osteoblastic cells. J. Nat. Med. 66(1), 8-16 (2012).
73. Kim HJ, Yoon KA, Lee MK, Kim SH, Lee IK, Kim SY. A novel small molecule, NecroX-7, inhibits osteoclast differentiation by suppressing NF-kappaB activity and c-Fos expression. Life Sci. 91(19-20), 928-934 (2012).
74. Urushibara M, Takayanagi H, Koga T et al. The antirheumatic drug leflunomide inhibits osteoclastogenesis by interfering with receptor activator of NF-kappa B ligand-stimulated induction of nuclear factor of activated T cells c1. Arthritis Rheum. 50(3), 794-804 (2004).
75. Kobayashi Y, Ueyama S, Arai Y et al. The active metabolite of leflunomide, A771726, inhibits both the generation of and the bone-resorbing activity of osteoclasts by acting directly on cells of the osteoclast lineage. J. Bone Mineral Metab. 22(4), 318-328 (2004).
76. Choi SH, Lee KR, Woo JC et al. Determination of a novel TAZ modulator, 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2́-(1H-tetrazole-5-yl) -biphenyl-4-ylmethyl] -3H imidazo[4,5-b]pyridine] (TM-25659) in rat plasma by liquid chromatography-tandem mass spectrometry. J. Pharm. Biomed. Anal. 63, 47-52 (2012).
77. Jang EJ, Jeong H, Kang JO et al. TM-25659 enhances osteogenic differentiation and suppresses adipogenic differentiation by modulating the transcriptional co-activator TAZ. Br. J. Pharmacol. 165(5), 1584-1594 (2012).
78. Li X, Yang J, He X et al. Identification of upregulators of BMP2 expression via high-throughput screening of a synthetic and natural compound library. J. Biomol. Screen. 14(10), 1251-1256 (2009).
79. Yamaguchi M, Moore TW, Sun A, Snyder JP, Shoji M. Novel curcumin analogue UBS109 potently stimulates osteoblastogenesis and suppresses osteoclastogenesis: Involvement in Smad activation and NF-kappaB inhibition. Integr. Biol. 4(8), 905-913 (2012).
80. Sangadala S, Boden SD, Viggeswarapu M, Liu Y, Titus L. LIM mineralization protein-1 potentiates bone morphogenetic protein responsiveness via a novel interaction with Smurf1 resulting in decreased ubiquitination of Smads. J. Biol. Chem. 281(25), 17212-17219 (2006).
81. Okada M, Sangadala S, Liu Y et al. Development and optimization of a cell-based assay for the selection of synthetic compounds that potentiate bone morphogenetic protein-2 activity. Cell Biochem. Func. 27(8), 526-534 (2009).
82. Kato S, Sangadala S, Tomita K, Titus L, Boden SD. A synthetic compound that potentiates bone morphogenetic protein-2-induced transdifferentiation of myoblasts into the osteoblastic phenotype. Mol. Cell. Biochem. 349(1-2), 97-106 (2011).
83. Rankin EB, Wu C, Khatri R et al. The HIF signaling pathway in osteoblasts directly modulates erythropoiesis through the production of EPO. Cell 149(1), 63-74 (2012).
84. Jones DT, Harris AL. Small-molecule inhibitors of the HIF pathway and synthetic lethal interactions. Exp. Opin. Ther. Targets 16(5), 463-480 (2012).
85. Scheuermann TH, Li Q, Ma HW et al. Allosteric inhibition of hypoxia inducible factor-2 with small molecules. Nat. Chem. Biol. 9(4), 271-276 (2013).
86. Correale M, Abruzzese S, Greco CA, Concilio M, Di Biase M, Brunetti ND. Statins in heart failure. Curr. Vasc. Pharmacol. (2012) (Epub ahead of print).
87. Liu J, Zhu LP, Yang XL, Huang HL, Ye DQ. HMG-CoA reductase inhibitors (statins) and bone mineral density: A meta-analysis. Bone 54(1), 151-156 (2013).
88. Maeda T, Matsunuma A, Kawane T, Horiuchi N. Simvastatin promotes osteoblast differentiation and mineralization in MC3T3-E1 cells. Biochem. Biophys. Res. Commun. 280(3), 874-877 (2001).
89. Kim HK, Cho SG, Kim JH et al. Mevinolin enhances osteogenic genes (ALP, type I collagen and osteocalcin), CD44, CD47 and CD51 expression during osteogenic differentiation. Life Sci. 84(9-10), 290-295 (2009).
90. Wang XH, Wang XK, Liang YJ et al. A cell-based screen for anticancer activity of 13 pyrazolone derivatives. Chin. J. Cancer 29(12), 980-987 (2010).
91. Barnett HA, Coe DM, Cooper TW et al. Aryl aminopyrazole benzamides as oral non-steroidal selective glucocorticoid receptor agonists. Bioorg. Med. Chem. Lett. 19(1), 158-162 (2009).
92. Castagnolo D, Manetti F, Radi M et al. Synthesis, biological evaluation, and SAR study of novel pyrazole analogues as inhibitors of Mycobacterium tuberculosis: Part 2. Synthesis of rigid pyrazolones. Bioorg. Med. Chem. 17(15), 5716-5721 (2009).
93. Lv HS, Han QQ, Ding XL et al. Synthesis and discovery of novel pyrazole carboxamide derivatives as potential osteogenesis inducers. Arch. Pharm. 345(11), 870-877 (2012).
94. Han QQ, Yu MJ, Ge SH et al. Osteopromotive activity of a novel pyrazole carboxamide derivative. Future Med. Chem. 5(2), 125-134 (2013).
95. Yadav DK, Gautam AK, Kureel J et al. Synthetic analogs of daidzein, having more potent osteoblast stimulating effect. Bioorg. Med. Chem. Lett. 21(2), 677-681 (2011).
96. Song D, Jiang X, Zhu S, Li W, Khadka A, Hu J. Denervation impairs bone regeneration during distraction osteogenesis in rabbit tibia lengthening. Acta Orthop. 83(4), 406-410 (2012).
97. Toops KA, Berlinicke C, Zack DJ, Nickells RW. Hydrocortisone stimulates neurite outgrowth from mouse retinal explants by modulating macroglial activity. Invest. Ophthalmol. Vis. Sci. 53(4), 2046-2061 (2012).
98. Parsons XH, Teng YD, Parsons JF, Snyder EY, Smotrich DB, Moore DA. Efficient derivation of human neuronal progenitors and neurons from pluripotent human embryonic stem cells with small molecule induction. J. Vis. Exp. 56, e3273 (2011).
99. Doorn J, Fernandes HA, Le BQ et al. A small molecule approach to engineering vascularized tissue. Biomaterials 34(12), 3053-3063 (2013).