Dihydrotestosterone and 17-Estradiol Enhancement of In Vitro Osteogenic Differentiation of Castrated Male Rat Bone Marrow Mesenchymal Stem Cells (rBMMSCs)
,
Abstract
Background: In vitro impact of dihydrotestosterone (DHT) and 17b-estradiol (E2) in osteogenic differentiation of castrated rat bone marrow mesenchymal stem cells (rBMMSC) still need to be clarified.
Materials and Methods: The viability, proliferation and density of cultured rBMMSC isolated from sham operated (Sham) and castrated (Cast) male rats were evaluated. rBMMSC were cultured with osteogenic differentiating medium (ODM) in the presence of DHT (5,10 nM) and E2 (10,100 nM). Osteogenesis was evaluated by alizarin red staining and measurement of calcium deposition and bone alkaline phosphatase (B-ALP) activity.
Results: Population doubling (PD) of rBMMSC isolated from Cast rats was significantly lower (P<0.05) compared to that isolated from Sham rats. rBMMSC from Cast rats showed low scattered calcified nodule after culturing in ODM and did not cause a significant increase in calcium deposition and B-ALP activity compared to rBMMSCs from Sham rats. Exposure of rBMMSC isolated from Cast rats to DHT (5 nM) or E2 (10 nM) in ODM showed medium scattered calcified nodules with significantly higher (P<0.05) calcium deposition and B-ALP activity. Moreover, exposure of rBMMSC to DHT (10 nM) or E2 (100 nM) showed high scattered calcified nodules with higher (P<0.01) calcium deposition and B-ALP activity
Conclusion: These results indicated that the presence of testes might participate in controlling the in vitro proliferation and osteogenic differentiation capacity of rBMMSCs. DHT and E2 can enhance the osteogenic capacity of rBMMSCs in a dose-dependent manner. Based on these observations, optimum usage of DHT and E2 can overcome the limitations of MSCs and advance the therapeutic bone regeneration potential in the future.
1. Logothetis C, Morris MJ, Den R, et al. Current perspectives on bone metastases in castrate-resistant prostate cancer. Cancer Metastasis Rev. 2018; 37(1):189-196.
2. Cauley JA, Cawthon PM, Peters KE, et al. Risk factors for hip fracture in older men: The osteoporotic fractures in men study (MrOS). J Bone Miner Res. 2016; 31(10):1810-1819.
3. Tewari D, Khan MP, Sagar N, et al. Ovariectomized rats with established osteopenia have diminished mesenchymal stem cells in the bone marrow and impaired homing, osteoinduction and bone regeneration at the fracture site. Stem Cell Rev Rep. 2015;11(2):309-21
4. Ryu SJ, Ryu DS, Kim JY, et al. Bone mineral density changes after orchiectomy using a scrotal approach in rats. Korean J Spine. 2015; 12(2):55-9.
5. Mori G, Brunetti G, Mastrangelo F, et al. Targeting Adult Mesenchymal Stem Cells Plasticity for Tissue Regeneration. Stem Cells Int. 2017; 2017: 4532179.
6. Kong L, Zhen LZ, Qin L, et al. Role of mesenchymal stem cells in osteoarthritis treatment. J OrthopTranslat. 2017; 9:89-103.
7. Manolagas SC. From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev. 2010; 31(3):266-300.
8. Huang CK, Lee SO, Lai KP, et al. Targeting androgen receptor in bone marrow mesenchymal stem cells leads to better transplantation therapy efficacy in liver cirrhosis.Hepatology. 2013; 57(4):1550-63.
9. Grumbach MM. Estrogen, bone, growth and sex: a sea change in conventional wisdom. J Pediatr Endocrinol Metab. 2000; 13 Suppl 6:1439-55.
10. Feng W, Cui Y, Song C, et al. Prevention of Osteoporosis and Hypogonadism by Allogeneic Ovarian Transplantation in Conjunction with Intra-Bone Marrow–Bone Marrow Transplantation. Transplantation. 2007; 84(11):1459-66.
11. Cauley JA. Estrogen and bone health in men and women. Steroids. 2015; 99(Pt A):11-5.
12. Ryu SJ, Ryu DS, Kim JY, et al. Changes in bone metabolism in young castrated male rats. Yonsei Med J. 2016; 57(6): 1386–1394.
13. Khanna-Jain R, Vuorinen A, Sándor GK, et al. Vitamin D3 metabolites induce osteogenic differentiation in human dental pulp and human dental follicle cells. J Steroid Biochem Mol Biol. 2010; 122(4):133-41.
14. Abo-Aziza FA, Zaki AA. The Impact of Confluence on Bone Marrow Mesenchymal Stem (BMMSC) Proliferation and Osteogenic Differentiation.Int J HematolOncol Stem Cell Res. 2017; 11(2):121-132.
15. Gurlek A, Pittelkow MR, Kumar R. Modulation of growth factor/cytokine synthesis and signaling by 1α, 25-dihydroxyvitamin D3: implications in cell growth and differentiation. Endocr Rev. 2002; 23(6):763-86.
16. Chang CY, Hsuuw YD, Huang FJ, et al. Androgenic and antiandrogenic effects and expression of androgen receptor in mouse embryonic stem cells. Fertil Steril. 2006; 85 Suppl 1:1195-203.
17. Crisostomo PR, Wang M, Herring CM, et al. Gender differences in injury induced mesenchymal stem cell apoptosis, expression of VEGF, TNF, and IL-6 and abrogation via TNFR1 ablation. J Mol Cell Cardiol. 2007; 42(1): 142–149.
18. Sinnesael M, Claessens F, Boonen S, et al. Novel insights in the regulation and mechanism of androgen action on bone. Curr Opin Endocrinol Diabetes Obes. 2013; 20(3):240-4.
19. Hofbauer LC, Hicok KC, Khosla S. Effects of gonadal and adrenal androgens in a novel androgen‐responsive human osteoblastic cell line. J Cell Biochem. 1998; 71(1):96-108.
20. Hong L, Zhang G, Sultana H, et al. The effects of 17-β estradiol on enhancing proliferation of human bone marrow mesenchymal stromal cells in vitro. Stem Cells Dev. 2011; 20(5):925-31.
21. Niada S, Giannasi C, Ferreira LM, et al. 17β-estradiol differently affects osteogenic differentiation of mesenchymal stem/stromal cells from adipose tissue and bone marrow. Differentiation. 2016; 92(5):291-297.
22. Corotchi MC, Popa MA, Simionescu M. Testosterone stimulates proliferation and preserves stemness of human adult mesenchymal stem cells and endothelial progenitor cells. Rom J Morphol Embryol. 2016; 57(1):75-80.
23. Wronski TJ, Lowry PL, Walsh CC, et al. Skeletal alterations in ovariectomized rats. Calcif Tissue Int. 1985; 37(3):324-8.
24. Eça LP, Ramalho RB, Oliveira IS, et al. Comparative study of technique to obtain stem cells from bone marrow collection between the iliac crest and the femoral epiphysis in rabbits. Acta Cir Bras. 2009; 24(5):400-4.
25. Gugjoo MB, Kinjavdekar AP, Aithal HP, et al. Isolation, culture and characterization of New Zealand White rabbit mesenchymal stem cells derived from bone marrow. X Asian J Anim Vet Adv. 2015; 10(10):537-48.
26. Akiyama K, You YO, Yamaza T, et al. Characterization of bone marrow derived mesenchymal stem cells in suspension. Stem Cell Res Ther. 2012; 3(5):40.
27. Ren J, Wang H, Tran K, et al. Human bone marrow stromal cell confluence: effects on cell characteristics and methods of assessment. Cytotherapy. 2015; 17(7):897-911.
28. Kang HY, Shyr CR, Huang CK, et al. Altered TNSALP expression and phosphate regulation contribute to reduced mineralization in mice lacking androgen receptor. Mol Cell Biol. 2008; 28(24):7354-67.
29. Salasznyk RM, Klees RF, Hughlock MK, et al. ERK signaling pathways regulate the osteogenic differentiation of human mesenchymal stem cells on collagen I and vitronectin. Cell Commun Adhes. 2004; 11(5-6):137-53.
30. Choi YS, Park SN, Suh H. Adipose tissue engineering using mesenchymal stem cells attached to injectable PLGA spheres. Biomaterials. 2005; 26(29):5855-63.
31. Oryana A, Kamali A, Moshiri A, et al. Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence? Cells Tissues Organs. 2017; 204(2):59-83.
32. Kosuke K, Terasaka T, Iwata N, et al. Combined Effects of Androgen and Growth Hormone on Osteoblast Marker Expression in Mouse C2C12 and MC3T3-E1 Cells Induced by Bone Morphogenetic Protein. J Clin Med. 2017; 6(1): 6.
33. Al-Mutairi KSH, Tariq IA, and Zaki AA. Osteogenic / Adipogenic Differentiation of Intact and Ovariectomized Young and Adult Female Rat Bone Marrow Mesenchymal Stem Cells (BMMSC). RJPBCS; 2019. 10(2): 253-265.
34. Dominici M, Paolucci P, Conte P, et al. Heterogeneity of multipotent mesenchymal stromal cells: from stromal cells to stem cells and vice versa. Transplantation. 2009; 87(9 Suppl):S36-42.
35. Russell KC, Lacey MR, Gilliam JK, et al. Clonal analysis of the proliferation potential of human bone marrow mesenchymal stem cells as a function of potency. Bio technol Bioeng. 2011; 108(11):2716-26.
36. Di Mambro A, Ferlin A, De Toni L, et al. Endothelial progenitor cells as a new cardiovascular risk factor in Klinefelter's syndrome. Mol Hum Reprod. 2010; 16(6):411-7.
37. Beck GR, Zerler B, Moran E. Phosphate is a specific signal for induction of osteopontin gene expression. Proc Natl Acad Sci U S A. 2000; 97(15): 8352–8357.
38. Suzuki A, Palmer G, Bonjour JP, et al. Stimulation of sodium‐dependent phosphate transport and signaling mechanisms induced by basic fibroblast growth factor in MC3T3‐E1 osteoblast‐like cells. J Bone Miner Res. 2000; 15(1):95-102.
39. Vanderschueren D, Van Herck E, Suiker AM, et al. Bone and mineral metabolism in aged male rats: short and long term effects of androgen deficiency. Endocrinology. 1992; 130(5):2906-16.
40. Greenspan SL, Neer RM, Ridgway EC, et al. Osteoporosis in men with hyperprolactinemic hypogonadism. Ann Intern Med. 1986; 104(6):777-82.
41. Stĕpán JJ, Lachman M, Zvĕrina J, et al. Castrated men exhibit bone loss: effect of calcitonin treatment on biochemical indices of bone remodeling. J Clin Endocrinol Metab. 1989; 69(3):523-7.
42. Aggarwal R, Lu J, Kanji S, et al. Human umbilical cord blood-derived CD34+ cells reverse osteoporosis in NOD/SCID mice by altering osteoblastic and osteoclastic activities. PLoS One. 2012; 7(6):e39365.
43. Wakley GK, Schutte HD Jr, Hannon KS, et al. Androgen treatment prevents loss of cancellous bone in the orchidectomized rat. J Bone Miner Res. 1991; 6(4):325-30.
44. Colvard DS, Eriksen EF, Keeting PE, et al. Identification of androgen receptors in normal human osteoblast-like cells. Proc Natl Acad Sci U S A. 1989; 86(3):854-7.
45. Vittek J, Altman K, Gordon GG, et al. The metabolism of 7α-3H-testosterone by rat mandibular bone. Endocrinology. 1974; 94(2):325-9.
46. Schweikert HU, Rulf W, Niederle N, et al. Testosterone metabolism in human bone. Acta Endocrinol (Copenh). 1980; 95(2):258-64.
47. Wang Q, Yu JH, Zhai HH, et al. Temporal expression of estrogen receptor alpha in rat bone marrow mesenchymal stem cells. Biochem Biophys Res Commun. 2006; 347(1):117-23.
48. Ge L, Cui Y, Cheng K, et al. Isopsoralen Enhanced Osteogenesis by Targeting AhR/ERα. Molecules. 2018; 23(10): 2600.
49. Berger MB, Cohen DJ, Olivares-Navarrete R, et al. Human osteoblasts exhibit sexual dimorphism in their response to estrogen on microstructured titanium surfaces. Biol Sex Differ. 2018; 9(1):30.
50. Hong L, Colpan A, Peptan IA. Modulations of 17-β estradiol on osteogenic and adipogenic differentiations of human mesenchymal stem cells. Tissue Eng. 2006; 12(10):2747-53.
51. Saito A, Nagaishi K, Iba K, et al. Umbilical cord extracts improve osteoporotic abnormalities of bone marrow-derived mesenchymal stem cells and promote their therapeutic effects on ovariectomised rats. Sci Rep. 2018; 8(1):1161.
52. Yuan FL, Xu RS, Jiang DL, et al. Leonurine hydrochloride inhibits osteoclastogenesis and prevents osteoporosis associated with estrogen deficiency by inhibiting the NF-κB and PI3K/Akt signaling pathways. Bone. 2015; 75:128-37.
53. Martin A, Xiong J, Koromila T, et al. Estrogens antagonize RUNX2-mediated osteoblast-driven osteoclastogenesis through regulating RANKL membrane association. Bone. 2015; 75:96-104.
54. Ayaloglu-Butun F, Terzioglu-Kara E, Tokcaer-Keskin Z, et al. The effect of estrogen on bone marrow-derived rat mesenchymal stem cell maintenance: inhibiting apoptosis through the expression of Bcl-x L and Bcl-2. Stem Cell Rev Rep. 2012; 8(2):393-401.
55. Chen FP, Hu CH, Wang KC. Estrogen modulates osteogenic activity and estrogen receptor mRNA in mesenchymal stem cells of women. Climacteric. 2013;16(1):154-60
56. Fan JZ, Yang L, Meng GL, et al. Estrogen improves the proliferation and differentiation of hBMSCs derived from postmenopausal osteoporosis through notch signaling pathway. Mol Cell Biochem. 2014; 392(1-2):85-93.
57. Song N, Wang ZM, He LJ, et al. Estradiol enhanced osteogenesis of rat bone marrow stromal cells is associated with the JNK pathway. Mol Med Rep. 2017; 16(6): 8589–8594.
58. Yatsu T, Kusakabe T, Kato K, et al. Selective Androgen Receptor Modulator, YK11, Up-Regulates Osteoblastic Proliferation and Differentiation in MC3T3-E1 Cells. Biol Pharm Bull. 2018; (3):394-398.
59. Chen Q, Kaji H, Kanatani M, et al. Testosterone increases osteoprotegerin mRNA expression in mouse osteoblast cells. Horm Metab Res. 2004; 36(10):674-8.
60. Kousteni S, Bellido T, Plotkin LI, et al. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell. 2001; 104(5):719-30.
61. Kang HY, Cho CL, Huang KL, et al. Nongenomic androgen activation of phosphatidylinositol 3‐kinase/Akt signaling pathway in MC3T3‐E1 osteoblasts. J Bone Miner Res. 2004; 19(7):1181-90.
2. Cauley JA, Cawthon PM, Peters KE, et al. Risk factors for hip fracture in older men: The osteoporotic fractures in men study (MrOS). J Bone Miner Res. 2016; 31(10):1810-1819.
3. Tewari D, Khan MP, Sagar N, et al. Ovariectomized rats with established osteopenia have diminished mesenchymal stem cells in the bone marrow and impaired homing, osteoinduction and bone regeneration at the fracture site. Stem Cell Rev Rep. 2015;11(2):309-21
4. Ryu SJ, Ryu DS, Kim JY, et al. Bone mineral density changes after orchiectomy using a scrotal approach in rats. Korean J Spine. 2015; 12(2):55-9.
5. Mori G, Brunetti G, Mastrangelo F, et al. Targeting Adult Mesenchymal Stem Cells Plasticity for Tissue Regeneration. Stem Cells Int. 2017; 2017: 4532179.
6. Kong L, Zhen LZ, Qin L, et al. Role of mesenchymal stem cells in osteoarthritis treatment. J OrthopTranslat. 2017; 9:89-103.
7. Manolagas SC. From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev. 2010; 31(3):266-300.
8. Huang CK, Lee SO, Lai KP, et al. Targeting androgen receptor in bone marrow mesenchymal stem cells leads to better transplantation therapy efficacy in liver cirrhosis.Hepatology. 2013; 57(4):1550-63.
9. Grumbach MM. Estrogen, bone, growth and sex: a sea change in conventional wisdom. J Pediatr Endocrinol Metab. 2000; 13 Suppl 6:1439-55.
10. Feng W, Cui Y, Song C, et al. Prevention of Osteoporosis and Hypogonadism by Allogeneic Ovarian Transplantation in Conjunction with Intra-Bone Marrow–Bone Marrow Transplantation. Transplantation. 2007; 84(11):1459-66.
11. Cauley JA. Estrogen and bone health in men and women. Steroids. 2015; 99(Pt A):11-5.
12. Ryu SJ, Ryu DS, Kim JY, et al. Changes in bone metabolism in young castrated male rats. Yonsei Med J. 2016; 57(6): 1386–1394.
13. Khanna-Jain R, Vuorinen A, Sándor GK, et al. Vitamin D3 metabolites induce osteogenic differentiation in human dental pulp and human dental follicle cells. J Steroid Biochem Mol Biol. 2010; 122(4):133-41.
14. Abo-Aziza FA, Zaki AA. The Impact of Confluence on Bone Marrow Mesenchymal Stem (BMMSC) Proliferation and Osteogenic Differentiation.Int J HematolOncol Stem Cell Res. 2017; 11(2):121-132.
15. Gurlek A, Pittelkow MR, Kumar R. Modulation of growth factor/cytokine synthesis and signaling by 1α, 25-dihydroxyvitamin D3: implications in cell growth and differentiation. Endocr Rev. 2002; 23(6):763-86.
16. Chang CY, Hsuuw YD, Huang FJ, et al. Androgenic and antiandrogenic effects and expression of androgen receptor in mouse embryonic stem cells. Fertil Steril. 2006; 85 Suppl 1:1195-203.
17. Crisostomo PR, Wang M, Herring CM, et al. Gender differences in injury induced mesenchymal stem cell apoptosis, expression of VEGF, TNF, and IL-6 and abrogation via TNFR1 ablation. J Mol Cell Cardiol. 2007; 42(1): 142–149.
18. Sinnesael M, Claessens F, Boonen S, et al. Novel insights in the regulation and mechanism of androgen action on bone. Curr Opin Endocrinol Diabetes Obes. 2013; 20(3):240-4.
19. Hofbauer LC, Hicok KC, Khosla S. Effects of gonadal and adrenal androgens in a novel androgen‐responsive human osteoblastic cell line. J Cell Biochem. 1998; 71(1):96-108.
20. Hong L, Zhang G, Sultana H, et al. The effects of 17-β estradiol on enhancing proliferation of human bone marrow mesenchymal stromal cells in vitro. Stem Cells Dev. 2011; 20(5):925-31.
21. Niada S, Giannasi C, Ferreira LM, et al. 17β-estradiol differently affects osteogenic differentiation of mesenchymal stem/stromal cells from adipose tissue and bone marrow. Differentiation. 2016; 92(5):291-297.
22. Corotchi MC, Popa MA, Simionescu M. Testosterone stimulates proliferation and preserves stemness of human adult mesenchymal stem cells and endothelial progenitor cells. Rom J Morphol Embryol. 2016; 57(1):75-80.
23. Wronski TJ, Lowry PL, Walsh CC, et al. Skeletal alterations in ovariectomized rats. Calcif Tissue Int. 1985; 37(3):324-8.
24. Eça LP, Ramalho RB, Oliveira IS, et al. Comparative study of technique to obtain stem cells from bone marrow collection between the iliac crest and the femoral epiphysis in rabbits. Acta Cir Bras. 2009; 24(5):400-4.
25. Gugjoo MB, Kinjavdekar AP, Aithal HP, et al. Isolation, culture and characterization of New Zealand White rabbit mesenchymal stem cells derived from bone marrow. X Asian J Anim Vet Adv. 2015; 10(10):537-48.
26. Akiyama K, You YO, Yamaza T, et al. Characterization of bone marrow derived mesenchymal stem cells in suspension. Stem Cell Res Ther. 2012; 3(5):40.
27. Ren J, Wang H, Tran K, et al. Human bone marrow stromal cell confluence: effects on cell characteristics and methods of assessment. Cytotherapy. 2015; 17(7):897-911.
28. Kang HY, Shyr CR, Huang CK, et al. Altered TNSALP expression and phosphate regulation contribute to reduced mineralization in mice lacking androgen receptor. Mol Cell Biol. 2008; 28(24):7354-67.
29. Salasznyk RM, Klees RF, Hughlock MK, et al. ERK signaling pathways regulate the osteogenic differentiation of human mesenchymal stem cells on collagen I and vitronectin. Cell Commun Adhes. 2004; 11(5-6):137-53.
30. Choi YS, Park SN, Suh H. Adipose tissue engineering using mesenchymal stem cells attached to injectable PLGA spheres. Biomaterials. 2005; 26(29):5855-63.
31. Oryana A, Kamali A, Moshiri A, et al. Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence? Cells Tissues Organs. 2017; 204(2):59-83.
32. Kosuke K, Terasaka T, Iwata N, et al. Combined Effects of Androgen and Growth Hormone on Osteoblast Marker Expression in Mouse C2C12 and MC3T3-E1 Cells Induced by Bone Morphogenetic Protein. J Clin Med. 2017; 6(1): 6.
33. Al-Mutairi KSH, Tariq IA, and Zaki AA. Osteogenic / Adipogenic Differentiation of Intact and Ovariectomized Young and Adult Female Rat Bone Marrow Mesenchymal Stem Cells (BMMSC). RJPBCS; 2019. 10(2): 253-265.
34. Dominici M, Paolucci P, Conte P, et al. Heterogeneity of multipotent mesenchymal stromal cells: from stromal cells to stem cells and vice versa. Transplantation. 2009; 87(9 Suppl):S36-42.
35. Russell KC, Lacey MR, Gilliam JK, et al. Clonal analysis of the proliferation potential of human bone marrow mesenchymal stem cells as a function of potency. Bio technol Bioeng. 2011; 108(11):2716-26.
36. Di Mambro A, Ferlin A, De Toni L, et al. Endothelial progenitor cells as a new cardiovascular risk factor in Klinefelter's syndrome. Mol Hum Reprod. 2010; 16(6):411-7.
37. Beck GR, Zerler B, Moran E. Phosphate is a specific signal for induction of osteopontin gene expression. Proc Natl Acad Sci U S A. 2000; 97(15): 8352–8357.
38. Suzuki A, Palmer G, Bonjour JP, et al. Stimulation of sodium‐dependent phosphate transport and signaling mechanisms induced by basic fibroblast growth factor in MC3T3‐E1 osteoblast‐like cells. J Bone Miner Res. 2000; 15(1):95-102.
39. Vanderschueren D, Van Herck E, Suiker AM, et al. Bone and mineral metabolism in aged male rats: short and long term effects of androgen deficiency. Endocrinology. 1992; 130(5):2906-16.
40. Greenspan SL, Neer RM, Ridgway EC, et al. Osteoporosis in men with hyperprolactinemic hypogonadism. Ann Intern Med. 1986; 104(6):777-82.
41. Stĕpán JJ, Lachman M, Zvĕrina J, et al. Castrated men exhibit bone loss: effect of calcitonin treatment on biochemical indices of bone remodeling. J Clin Endocrinol Metab. 1989; 69(3):523-7.
42. Aggarwal R, Lu J, Kanji S, et al. Human umbilical cord blood-derived CD34+ cells reverse osteoporosis in NOD/SCID mice by altering osteoblastic and osteoclastic activities. PLoS One. 2012; 7(6):e39365.
43. Wakley GK, Schutte HD Jr, Hannon KS, et al. Androgen treatment prevents loss of cancellous bone in the orchidectomized rat. J Bone Miner Res. 1991; 6(4):325-30.
44. Colvard DS, Eriksen EF, Keeting PE, et al. Identification of androgen receptors in normal human osteoblast-like cells. Proc Natl Acad Sci U S A. 1989; 86(3):854-7.
45. Vittek J, Altman K, Gordon GG, et al. The metabolism of 7α-3H-testosterone by rat mandibular bone. Endocrinology. 1974; 94(2):325-9.
46. Schweikert HU, Rulf W, Niederle N, et al. Testosterone metabolism in human bone. Acta Endocrinol (Copenh). 1980; 95(2):258-64.
47. Wang Q, Yu JH, Zhai HH, et al. Temporal expression of estrogen receptor alpha in rat bone marrow mesenchymal stem cells. Biochem Biophys Res Commun. 2006; 347(1):117-23.
48. Ge L, Cui Y, Cheng K, et al. Isopsoralen Enhanced Osteogenesis by Targeting AhR/ERα. Molecules. 2018; 23(10): 2600.
49. Berger MB, Cohen DJ, Olivares-Navarrete R, et al. Human osteoblasts exhibit sexual dimorphism in their response to estrogen on microstructured titanium surfaces. Biol Sex Differ. 2018; 9(1):30.
50. Hong L, Colpan A, Peptan IA. Modulations of 17-β estradiol on osteogenic and adipogenic differentiations of human mesenchymal stem cells. Tissue Eng. 2006; 12(10):2747-53.
51. Saito A, Nagaishi K, Iba K, et al. Umbilical cord extracts improve osteoporotic abnormalities of bone marrow-derived mesenchymal stem cells and promote their therapeutic effects on ovariectomised rats. Sci Rep. 2018; 8(1):1161.
52. Yuan FL, Xu RS, Jiang DL, et al. Leonurine hydrochloride inhibits osteoclastogenesis and prevents osteoporosis associated with estrogen deficiency by inhibiting the NF-κB and PI3K/Akt signaling pathways. Bone. 2015; 75:128-37.
53. Martin A, Xiong J, Koromila T, et al. Estrogens antagonize RUNX2-mediated osteoblast-driven osteoclastogenesis through regulating RANKL membrane association. Bone. 2015; 75:96-104.
54. Ayaloglu-Butun F, Terzioglu-Kara E, Tokcaer-Keskin Z, et al. The effect of estrogen on bone marrow-derived rat mesenchymal stem cell maintenance: inhibiting apoptosis through the expression of Bcl-x L and Bcl-2. Stem Cell Rev Rep. 2012; 8(2):393-401.
55. Chen FP, Hu CH, Wang KC. Estrogen modulates osteogenic activity and estrogen receptor mRNA in mesenchymal stem cells of women. Climacteric. 2013;16(1):154-60
56. Fan JZ, Yang L, Meng GL, et al. Estrogen improves the proliferation and differentiation of hBMSCs derived from postmenopausal osteoporosis through notch signaling pathway. Mol Cell Biochem. 2014; 392(1-2):85-93.
57. Song N, Wang ZM, He LJ, et al. Estradiol enhanced osteogenesis of rat bone marrow stromal cells is associated with the JNK pathway. Mol Med Rep. 2017; 16(6): 8589–8594.
58. Yatsu T, Kusakabe T, Kato K, et al. Selective Androgen Receptor Modulator, YK11, Up-Regulates Osteoblastic Proliferation and Differentiation in MC3T3-E1 Cells. Biol Pharm Bull. 2018; (3):394-398.
59. Chen Q, Kaji H, Kanatani M, et al. Testosterone increases osteoprotegerin mRNA expression in mouse osteoblast cells. Horm Metab Res. 2004; 36(10):674-8.
60. Kousteni S, Bellido T, Plotkin LI, et al. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell. 2001; 104(5):719-30.
61. Kang HY, Cho CL, Huang KL, et al. Nongenomic androgen activation of phosphatidylinositol 3‐kinase/Akt signaling pathway in MC3T3‐E1 osteoblasts. J Bone Miner Res. 2004; 19(7):1181-90.
| Files | ||
| Issue | Vol 13, No 4 (2019) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v13i4.1897 | |
| Keywords | ||
| rBMMSC; Dihydrotestosterone; 17-estradiol; Osteogenesis; Castration | ||
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How to Cite
1.
Abo-Aziza F, Zaki A, Amer A, Lotfy R. Dihydrotestosterone and 17-Estradiol Enhancement of In Vitro Osteogenic Differentiation of Castrated Male Rat Bone Marrow Mesenchymal Stem Cells (rBMMSCs). Int J Hematol Oncol Stem Cell Res. 2019;13(4):208-219.
