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http://dx.doi.org/10.12717/DR.2013.17.4.299

$PKC{\eta}$ Regulates the $TGF{\beta}3$-induced Chondrogenic Differentiation of Human Mesenchymal Stem Cell  

Ku, Bo Mi (Department of Anatomy & Neurobiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University)
Yune, Young Phil (Department of Anatomy & Neurobiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University)
Lee, Eun Shin (Department of Rehabilitation Medicine, School of Medicine, Gyeongsang National University)
Hah, Young-Sool (Clinical Research Institute, Gyeongsang National University Hospital)
Park, Jae Yong (Dept. of Physiology, School of Medicine, Gyeongsang National University)
Jeong, Joo Yeon (Department of Anatomy & Neurobiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University)
Lee, Dong Hoon (Department of Anatomy & Neurobiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University)
Cho, Gyeong Jae (Department of Anatomy & Neurobiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University)
Choi, Wan Sung (Department of Anatomy & Neurobiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University)
Kang, Sang Soo (Department of Anatomy & Neurobiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University)
Publication Information
Development and Reproduction / v.17, no.4, 2013 , pp. 299-309 More about this Journal
Abstract
Transforming growth factor (TGF) family is well known to induce the chondrogenic differentiation of mesenchymal stem cells (MSC). However, the precise signal transduction pathways and underlying factors are not well known. Thus the present study aims to evaluate the possible role of C2 domain in the chondrogenic differentiation of human mesenchymal stem cells. To this end, 145 C2 domains in the adenovirus were individually transfected to hMSC, and morphological changes were examined. Among 145 C2 domains, C2 domain of protein kinase C eta ($PKC{\eta}$) was selected as a possible chondrogenic differentiation factor for hMSC. To confirm this possibility, we treated $TGF{\beta}3$, a well known chondrogenic differentiation factor of hMSC, and examined the increased-expression of glycosaminoglycan (GAG), collagen type II (COL II) as well as $PKC{\eta}$ using PT-PCR, immunocytochemistry and Western blot analysis. To further evaluation of C2 domain of $PKC{\eta}$, we examined morphological changes, expressions of GAG and COL II after transfection of $PKC{\eta}$-C2 domain in hMSC. Overexpression of $PKC{\eta}$-C2 domain induced morphological change and increased GAG and COL II expressions. The present results demonstrate that $PKC{\eta}$ involves in the TGF-${\beta}3$-induced chondrogenic differentiation of hMSC, and C2 domain of $PKC{\eta}$ has important role in this process.
Keywords
Human mesenchymal stem cell; Chondrogenesis; TGF-${\beta}3$; $PKC{\eta}$; C2-domain;
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1 Hellingman CA, Davidson EN, Koevoet W, Vitters EL, van den Berg WB, van Osch GJ, van der Kraan PM (2011) Smad signaling determines chondrogenic differentiation of bone-marrow-derived mesenchymal stem cells: inhibition of Smad1/5/8P prevents terminal differentiation and calcification. Tissue Eng Part A 17: 1157-1167.   DOI   ScienceOn
2 Huang AH, Farrell MJ, Mauck RL (2010) Mechanics and mechanobiology of mesenchymal stem cell-based engineered cartilage. J Biomech 43:128-136.   DOI   ScienceOn
3 Jin EJ, Park KS, Kim D, Lee YS, Sonn JK, Jung JC, Bang OS, Kang SS (2010) TGF-beta3 inhibits chondrogenesis by suppressing precartilage condensation through stimulation of N-cadherin shedding and reduction of cRREB-1 expression. Mol Cells 29:425-432.   DOI   ScienceOn
4 Jo J, Lee Y, Oh MH, Ko JJ, Cheon Y-P, Lee DR (2010) Up-regulation of pluripotency-related genes in human amniotic fluid-derived stem cells by ESRRB conjugated with cell-penetrating peptide. Dev Reprod 14:243-251.
5 Karsenty G, Wagner EF (2002) Reaching a genetic and molecular understanding of skeletal development. Dev Cell 2:389-406.   DOI   ScienceOn
6 Kashiwagi M, Ohba M, Chida K, Kuroki T (2002) Protein kinase C eta (PKC eta): its involvement in keratinocyte differentiation. J Biochem 132:853-857.   DOI   ScienceOn
7 Kawakami Y, Rodriquez-Leon J, Izpisua Belmonte JC (2006) The role of TGFbetas and Sox9 during limb chondrogenesis. Curr Opin Cell Biol 18:723-729.   DOI   ScienceOn
8 Lampasso JD, Chen W, Marzec N (2006) The expression profile of PKC isoforms during MC3T3-E1 differentiation. Int J Mol Med 17:1125-1131.
9 Lee HK, Yeo S, Kim JS, Lee JG, Bae YS, Lee C, Baek SH (2010) Protein kinase C-eta and phospholipase D2 pathway regualates foam cell formation via regulator of G protein signaling 2. Mol Pharmacol 78:478-485.   DOI   ScienceOn
10 Li J, Zhao Z, Liu J, Huang N, Long D, Wang J, Li X, Liu Y (2010) MEK/ERK and p38 MAPK regulate chondrogenesis of rat bone marrow mesenchymal stem cells through delicate interaction with TGF-beta1/ Smads pathway. Cell Prolif 43:333-343.   DOI   ScienceOn
11 Adhikary G, Chew YC, Reece EA, Eckert RL (2010) PKC-delta and-eta, MEKK-1, MEK-6, MEK-3, and p38-delta are essential mediators of the response of normal human epidermal keratinocytes to differentiating agents. J Invest Dermatol 130:2017-2030.   DOI   ScienceOn
12 Augello A, De Bari C (2010) The regulation of differentiation in mesenchymal stem cells. Hum Gnen Ther 21:1226-1238.   DOI   ScienceOn
13 Bobick BE, Chen FH, Le AM, Tuan RS (2009) Regulation of the chondrogenic phenotype in culture. Brith Defects Res CEmbryo Today 87:351-371.   DOI   ScienceOn
14 Boeuf S, Richter W (2010) Chondrogenesis of mesenchymal stem cells: role of tissue source and inducing factors. Stem Cell Res Ther 1:31.   DOI   ScienceOn
15 Chen WH, Lai MT, Wu AT, Wu CC, Gelovani JG, Lin CT, Hung SC, Chiu WT, Deng WP (2009) In vitro stage-specific chondrogenesis of mesenchymal stem cells committed to chondrocytes. Arthritis Rheum 60:450-459.   DOI   ScienceOn
16 Corbalan-Garcia S, Gomez-Fernandez JC (2010) The C2 domains of classical and nobel PKCs as versatile decoders of membrane signals. Biofactors 36:1-7.
17 Csaki C, Schneider PR, Shakibaei M (2008) Mesenchymal stem cells as a potential pool for cartilage tissue engineering. Ann Anat 190:395-412.   DOI   ScienceOn
18 de Crombrugghe B, Lefebvre V, Behringer RR, Bi W, Murakami S, Huang W (2000) Transcriptional mechanisms of chondrocyte differentiation. Matrix Biol 19:389-394.   DOI   ScienceOn
19 Shtutman M, Hershko T, Maissel A, Fima E, Livneh E (2003) PKCeta associates with cyclin E/Cdk2 complex in serum-starved MCR-7 and NIH-3T3 cells. Exp Cell Res 286:22-29.   DOI   ScienceOn
20 Sang Y, Zang W, Yan Y, Liu Y, Fu Q, Wang K, Chen Y, Qi N (2014) Study of differential effects of TGFbeta3/ BMP2 on chondrogenesis in MSC cells by gene microarray data analysis. Mol Cell Biochem 385:191-198.   DOI   ScienceOn
21 Shum L, Nuckolls G (2002) The life cycle of chondrocytes in the developing skeleton. Arthritis Res 4:94-106.
22 Vater C, Kasten P, Stiehler M (2011) Culture media for the differentiation of mesenchymal stromal cells. Acta Biomater 7:463-377.   DOI   ScienceOn
23 Zhang L, Su P, Xu C, Yang J, Yu W, Huang D (2010) Chondrogenic differentiation of human mesenchymal stem cells: a comparison between micromass and pellet culture systems. Biotechnol Lett 32(9):1339-1346.   DOI   ScienceOn
24 Wang Y, Belflower RM, Dong YF, Schwarz EM, O'Keefe RJ, Drissi H (2005) Runx1/AML1/Cbfa2 mediates onset of mesenchymal cell differentiation toward chondrogenesis. J Bone Miner Res 20:1624-1636.   DOI   ScienceOn
25 Woods A, Wang G, Beier F (2007) Regulation of chondrocyte differentiation by the actin cytoskeleton and adhesive interactions. J Cell Physiol 213:1-8.   DOI   ScienceOn
26 Woods A, Wang G, Dupuis H, Shao Z, Beier F (2007) Rac1 signaling stimulated N-cadherin expression, mesenchymal condensation, and chondrogenesis. J Biol Chem 282:23500-23508.   DOI   ScienceOn
27 Littler DR, Walker JR, She YM, Finerty PJJr, Newman EM, Dhe-Paganon S (2006) Structure of human protein kinase C eta (PKCeta) C2 domain and identification of phosphorylation sites. Biochem Biophys Res Commun 349:1182-1189.   DOI   ScienceOn
28 Matta C, Juhasz T, Szijgyarto Z, Kolozsvari B, Somogyi C, Nagy G, Gergely P, Zakany R (2011) PKCdelta is a positive regulator of chondrogenesis in chicken high density micromass cell cultures. Biochimie 93: 149-159.   DOI   ScienceOn
29 Newton AC (1997) Regulation of protein kinase C. Curr Opin Cell Biol 9:161-167.   DOI   ScienceOn
30 Muir H (1995) The chondrocyte, architect of cartilage. Biomechanics, structure, function and molecular biology of cartilage matrix macromolecules. Bioessays 17:1039- 1048.   DOI
31 Nochi H, Sung JH, Lou J, Adkisson HD, Maloney WJ, Hruska KA (2004) Adenovirus mediated BMP-13 gene transfer induces chondrogenic differentiation of murine mesenchymal progenitor cells. J Bone Miner Res 19:111-122.   DOI   ScienceOn
32 Park JY, Hwang EM, Park N, Kim E, Kim DG, Kang D, Han J, Choi WS, Ryu PD, Hong SG (2007) Gateway RFP-fusion vectors for high throughput functional analysis of genes. Mol Cells 23:357-362.
33 Pelttari K, Steck E, Richter W (2008) The use of mesenchymal stem cells for chondrogenesis. Injury 39(Suppl 1):S58-65.   DOI   ScienceOn
34 Pelttari K, Winter A, Steck E, Goetzke K, Hennig T, Ochs BG, Aigner T, Richter W (2006) Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice. Arthritis Rheum 54:3254-3266.   DOI   ScienceOn
35 Rosse C, Linch M, Kermorgant S, Cameron AJ, Boeckeler K, Parker PJ (2010) PKC and the control of localized signal dynamics. Nat Rev Mol Cell Biol 11:103-112.   DOI   ScienceOn
36 Rotem-Dai N, Oberkovitz G, Abu-Ghanem S, Livneh E (2009) PKCeta confers protection against apoptosis by inhibiting the pro-apoptotic JNK activity in MCF-7 cells. Exp Cell Res 315:2616-2623.   DOI   ScienceOn
37 Sandell LJ, Aigner T (2001) Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis. Arthritis Res 3:107-113.   DOI   ScienceOn
38 DiNitto JP, Cronin TC, Lambright DG (2003) Membrane recognition and targeting by lipid-binding domains. Sci STKE 2003 (213):re16.
39 Fong EL, Chan CK, Goodman SB (2010) Stem cell homing in musculoskeletal injury. Biomaterials 32:395-409.
40 Arita NA, Pelaez D, Cheung HS (2011) Activation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) is needed for the TGF$\beta$-induced chondrogenic and osteogenic differentiation of mesenchymal stem cells. Biochem Biophys Res Commun 405:564-569.   DOI   ScienceOn
41 Nishizuka Y (1992) Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science 258:607-614.   DOI