Porcine placenta extract induced Akt, ERK, and JNK signaling to heighten the osteogenic activity of human osteoblasts

Worawat Songjang Chatchai Nensat Rutaiwan Tohtong Tuangporn Suthiphongchai Suchada Phimsen Panthip Rattanasinganchan Pornphimon Metheenukul Waraporn Kasekarn and Arunya Jiraviriyakul   

Open Access   

Published:  Jun 13, 2022


Porcine placenta extract (PPE) is an effective pharmaceutical and cosmetic ingredient, despite its high bioavailability. Despite this, only a few studies on the extract’s effect on human osteoblast cellular behavior have been conducted. This study used hFOB 1.19 cells to demonstrate the mechanism by which a novel potent osteogenic compound that was discovered by stimulating the growth, alkaline phosphatase secretion, mineralization, and osteogenesis markers of human osteoblast hFOB 1.19 cells resulted in significant increases in extracellular signal-regulated kinase (ERK)1/2, Akt, and c-Jun N-terminal kinase (JNK) phosphorylation. In addition, PPE was discovered to significantly increase in vitro bone formation that may provide the beneficial potential for osteoporosis prevention and treatment.

Keyword:     Placenta extract porcine osteoblast ontogenesis osteoporosis.


Songjang W, Nensat C, Tohtong R, Suthiphongchai T, Phimsen S, Rattanasinganchan P, Metheenukul P, Kasekarn W, Jiraviriyakul A. Porcine placenta extract induced Akt, ERK, and JNK signaling to heighten the osteogenic activity of human osteoblasts. J Appl Pharm Sci, 2022. Online First.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature, 2003; 423:337-42. https://doi.org/10.1038/nature01658

Choi KY, Kim HJ, Lee MH, Kwon TG, Nah HD, Furuichi T, Komori T, Nam SH, Kim YJ, Kim HJ, Ryoo HM. Runx2 regulates FGF2- induced Bmp2 expression during cranial bone development. Dev Dyn, 2005; 233:115-21. https://doi.org/10.1002/dvdy.20323

Cross JC. Adaptability and potential for treatment of placental functions to improve embryonic development and postnatal health. Reprod Fertil Dev, 2016; 28:75-82. https://doi.org/10.1071/RD15342

Curtis EM, Moon RJ, Dennison EM, Harvey NC, Cooper C. Recent advances in the pathogenesis and treatment of osteoporosis. Clin Med (Lond), 2015; 15 Suppl 6:s92-6. https://doi.org/10.7861/clinmedicine.15-6-s92

Ducy P, Schinke T, Karsenty G. The osteoblast: a sophisticated fibroblast under central surveillance. Science, 2000; 289:1501-4. https://doi.org/10.1126/science.289.5484.1501

Ghosh-Choudhury N, Abboud SL, Nishimura R, Celeste A, Mahimainathan L, Choudhury GG. Requirement of BMP-2-induced phosphatidylinositol 3-kinase and Akt serine/threonine kinase in osteoblast differentiation and Smad-dependent BMP-2 gene transcription. J Biol Chem, 2002; 277:33361-8. https://doi.org/10.1074/jbc.M205053200

Heo JH, Heo Y, Lee HJ, Kim M, Shin HY. Topical antiinflammatory and anti-oxidative effects of porcine placenta extracts on 2,4-dinitrochlorobenzene-induced contact dermatitis. BMC Complement Altern Med, 2018; 18:331. https://doi.org/10.1186/s12906-018-2396-1

Hidaka K, Kanematsu T, Takeuchi H, Nakata M, Kikkawa U, Hirata M. Involvement of the phosphoinositide 3-kinase/protein kinase B signaling pathway in insulin/IGF-I-induced chondrogenesis of the mouse embryonal carcinoma-derived cell line ATDC5. Int J Biochem Cell Biol, 2001; 33:1094-103. https://doi.org/10.1016/S1357-2725(01)00067-X

Imamura Y, Honda Y, Masuno K, Nakamura H, Wang P-L. Effects of placental extract on cell proliferation, type i collagen production, and ALP secretion in human osteosarcoma cell line Saos-2. J Hard Tissue Biol, 2017; 26:157-60. https://doi.org/10.2485/jhtb.26.157

Kapila V, Chaudhry K. Physiology, placenta. In StatPearls. StatPearls Publishing, Treasure Island, FL, 2021.

Kim HJ, Rice DP, Kettunen PJ, Thesleff I. FGF-, BMP- and Shh-mediated signalling pathways in the regulation of cranial suture morphogenesis and calvarial bone development. Development, 1998; 125:1241-51. https://doi.org/10.1242/dev.125.7.1241

Kim MH, Kim K, Lee H, Yang WM. Human placenta induces hair regrowth in chemotherapy-induced alopecia via inhibition of apoptotic factors and proliferation of hair follicles. BMC Complement Med Ther, 2020; 20:230. https://doi.org/10.1186/s12906-020-03025-z

King AE, Paltoo A, Kelly RW, Sallenave JM, Bocking AD, Challis JRG. Expression of natural antimicrobials by human placenta and fetal membranes. Placenta, 2007; 28:161-9. https://doi.org/10.1016/j.placenta.2006.01.006

Kudo Y, Iwashita M, Iguchi T, Takeda Y. The regulation of type-I collagen synthesis by insulin-like growth factor-I in human osteoblast-like SaOS-2 cells. Pflugers Arch, 1996; 433:123-8. https://doi.org/10.1007/s004240050257

Lee HY, Chae HJ, Park SY, Kim JH. Porcine placenta hydrolysates enhance osteoblast differentiation through their antioxidant activity and effects on ER stress. BMC Complement Altern Med, 2016; 16:291. https://doi.org/10.1186/s12906-016-1274-y

Lee KH, Park HJ, Seo HG, Kim JH, Lim GS, Lee WY, Kim NH, Kim JH, Lee JH, Jung HS, Sung SH, Song H. Immune modulation effect of porcine placenta extracts in weaned the pig. J Anim Sci, 2013; 91:2405-13. https://doi.org/10.2527/jas.2012-5208

Lee M-H, Kwon T-G, Park H-S, Wozney JM, Ryoo H-M. BMP2-induced Osterix expression is mediated by Dlx5 but is independent of Runx2. Biochem Biophys Res Commun, 2003; 309:689-94. https://doi.org/10.1016/j.bbrc.2003.08.058

Li X, Ling W, Pennisi A, Wang Y, Khan S, Heidaran M, Pal A, Zhang X, He S, Zeitlin A, Abbot S, Faleck H, Hariri R, Shaughnessy JD Jr, van Rhee F, Nair B, Barlogie B, Epstein J, Yaccoby S. Human placentaderived adherent cells prevent bone loss, stimulate bone formation, and suppress growth of multiple myeloma in bone. Stem cells (Dayton, Ohio), 2011; 29:263-73. https://doi.org/10.1002/stem.572

Maruyama Z, Yoshida CA, Furuichi T, Amizuka N, Ito M, Fukuyama R, Miyazaki T, Kitaura H, Nakamura K, Fujita T, Kanatani N, Moriishi T, Yamana K, Liu W, Kawaguchi H, Nakamura K, Komori T. Runx2 determines bone maturity and turnover rate in postnatal bone development and is involved in bone loss in estrogen deficiency. Dev Dyn, 2007; 236:1876-90. https://doi.org/10.1002/dvdy.21187

Nagae M, Nagata M, Teramoto M, Yamakawa M, Matsuki T, Ohnuki K, Shimizu K. Effect of porcine placenta extract supplement on skin condition in healthy adult women: a randomized, double-blind placebocontrolled study. Nutrients, 2020; 12:1671. https://doi.org/10.3390/nu12061671

Nensat C, Songjang W, Tohtong R, Suthiphongchai T, Phimsen S, Rattanasinganchan P, Metheenukul P, Kumphune S, Jiraviriyakul A. Porcine placenta extract improves high-glucose-induced angiogenesis impairment. BMC Complement Med Ther, 2021; 21:66. https://doi.org/10.1186/s12906-021-03243-z

Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, Stamp GW, Beddington RS, Mundlos S, Olsen BR, Selby PB, Owen MJ. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell, 1997; 89:765-71. https://doi.org/10.1016/S0092-8674(00)80259-7

Padhomchai Pumbthongthae PH, Roytrakul S, Janvilisri T, Ounjai P. Analysis of protein profile of crude porcine placenta extract. In: The 50th National Graduate Research Conference. King Mongkut's Institute of Technology Ladkrabang, Bangkok, Thailand, 2020.

Park KM, Cho TH. Therapeutic effect of acupuncture point injection with placental extract in knee osteoarthritis. J Integr Med, 2017; 15:135-41. https://doi.org/10.1016/S2095-4964(17)60316-9

Park O-J, Kim H-J, Woo K-M, Baek J-H, Ryoo H-M. FGF2- activated ERK mitogen-activated protein kinase enhances Runx2 acetylation and stabilization*. J Biol Chem, 2010; 285:3568-74. https://doi.org/10.1074/jbc.M109.055053

Peng XD, Xu PZ, Chen ML, Hahn-Windgassen A, Skeen J, Jacobs J, Sundararajan D, Chen WS, Crawford SE, Coleman KG, Hay N. Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2. Genes Dev, 2003; 17:1352-65. https://doi.org/10.1101/gad.1089403

Phuapradit W, Chanrachakul B, Thuvasethakul P, Leelaphiwat S, Sassanarakkit S, Chanworachaikul S. Nutrients and hormones in heat-dried human placenta. J Med Assoc Thai, 2000; 83:690-4.

Rachner TD, Khosla S, Hofbauer LC. Osteoporosis: now and the future. Lancet, 2011; 377:1276-87. https://doi.org/10.1016/S0140-6736(10)62349-5

Rozanova S, Cherkashina Y, Repina S, Rozanova K, Nardid O. Protective effect of placenta extracts against nitrite-induced oxidative stress in human erythrocytes. Cell Mol Biol Lett, 2012; 17:240-8. https://doi.org/10.2478/s11658-012-0007-6

Schulman RC, Weiss AJ, Mechanick JI. Nutrition, bone, and aging: an integrative physiology approach. Curr Osteoporos Rep, 2011; 9:184-95. https://doi.org/10.1007/s11914-011-0079-7

Shukla VK, Rasheed MA, Kumar M, Gupta SK, Pandey SS. A trial to determine the role of placental extract in the treatment of chronic non-healing wounds. J Wound Care, 2004; 13:177-9. https://doi.org/10.12968/jowc.2004.13.5.26668

Xu R, Zhang C, Shin DY, Kim JM, Lalani S, Li N, Yang YS, Liu Y, Eiseman M, Davis RJ, Shim JH, Greenblatt MB. c-Jun N-terminal kinases (JNKs) are critical mediators of osteoblast activity in vivo. J Bone Miner Res, 2017; 32:1811-5. https://doi.org/10.1002/jbmr.3184

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