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Anatomical Science International

Erschienen in:

16.12.2016 | Review Article

Roles of PKR in differentiation and apoptosis of bone-related cells

verfasst von: Tatsuji Haneji

Erschienen in: Anatomical Science International | Ausgabe 3/2017

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Abstract

Double-stranded RNA-dependent protein kinase (PKR) is a serine/threonine protein kinase which is activated by double-stranded RNAs and related to several signal transduction pathways. To examine the effects of PKR on bone metabolism, we established PKR-K/R mutant cells in which amino acid lysine at 296 is substituted with arginine. PKR regulated apoptosis in osteoblastic cells via nuclear factor kappa-B (NF-κB) cascade. MC3T3-E1 cells cultured with osteoblast differentiation medium differentiated into osteoblasts, while the mutant cells did not differentiate into osteoblasts. RAW246.7 cells triggered with receptor activator of NF-κB ligand (RANKL) formed tartrate-resistant acid phosphatase-positive multinucleated giant cells, whereas PKR-K/R mutant RAW cells did not. Differentiation of osteoblasts and osteoclasts was caused by NF-κB activation and signal transducer and activator of transcription 1 (STAT1) ubiquitination and degradation. We also demonstrated involvement of PKR in chondrocyte differentiation. PKR prevented tumor necrosis factor-α- and interleukin 1α-induced bone resorption in calvaria and artificially induced periodontal disease in rat. Our findings indicate that PKR regulates bone metabolism in vitro and in vivo.

Alisi A, Spaziani A, Anticoli S, Ghidinelli M, Balsano C (2008) PKR is a novel functional direct player that coordinates skeletal muscle differentiation via p38 MAPK/AKT pathways. Cell Signal 20:534–542CrossRefPubMed

André ND, Silva VA, Watanabe MA, De Lucca FL (2014) Intratumoral injection of PKR shRNA expressing plasmid inhibits B16-F10 melanoma growth. Oncol Rep 32:2267–2273PubMed

Atsumi T, Miwa Y, Kimata K, Ikawa Y (1990) A chondrogenic cell line derived from a differentiating culture of AT805 teratocarcinoma cells. Cell Differ Dev 30:109–116CrossRefPubMed

Boyce BE (2013) Advances in the regulation of osteoclasts and osteoclast function. J Dent Res 92:860–867CrossRefPubMedPubMedCentral

Bruderer M, Richards RG, Alini M, Stoddart MJ (2014) Role and regulation of RUNX2 in osteogenesis. Eur Cell Mater 28:269–286CrossRefPubMed

Capulli M, Paone R, Rucci N (2014) Osteoblast and osteocyte: games without frontiers. Arch Biochem Biophys 561:3–12CrossRefPubMed

Chaman N, Iqbal MA, Siddiqui FA, Gopinath P, Bamezai RN (2015) ERK2-Pyruvate kinase axis permits phorbol 12-myristate 13-acetate-induced megakaryocyte differentiation in K562 cells. J Biol Chem 290:23803–23815CrossRefPubMedPubMedCentral

Chiu YH, Ritchlin CT (2016) DC-STAMP: a key regulator in osteoclast differentiation. J Cell Physiol 231:2402–2407CrossRefPubMedPubMedCentral

Cross TG, Scheel-Toellner D, Henriquz NV, Deacon E, Salmon M, Lord JM (2000) Serine/threonine protein kinases and apoptosis. Exp Cell Res 256:34–41CrossRefPubMed

Dalet A, Gatti E, Pierre P (2015) Integration of PKR-dependent translation inhibition with innate immunity is required for a coordinated anti-viral response. FEBS Lett 589:1539–1545CrossRefPubMed

Donnelly N, Gorman AM, Gupta S, Samali A (2013) The eIF2α kinases: their structures and functions. Cell Mol Life Sci 70:3493–3511CrossRefPubMed

Drissi H, Sanjay A (2016) The multifaceted osteoclast; far and beyond bone resorption. J Cell Biochem 171:1753–1756CrossRef

Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G (1997) Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89:747–754CrossRefPubMed

Fernandez JJ, Candenas ML, Souto ML, Trujillo MM, Norte M (2002) Okadaic acid, useful tool for studying cellular processes. Curr Med Chem 9:229–262CrossRefPubMed

Gil J, Esteban M (2000) Induction of apoptosis by the dsRNA-dependent protein kinase (PKR): mechanism of action. Apoptosis 5:107–114CrossRefPubMed

Gilbert SJ, Blain EJ, Al-Sabah A, Zhang Y, Duance VC, Mason DJ (2012) Protein kinase R plays a pivotal role in oncostatin M and interleukin-1 signalling in bovine articular cartilage chondrocytes. Eur Cell Mater 23:41–57CrossRefPubMed

Ha H, Lee LH, Kim HN, Kwak HB, Kim HM, Lee SE, Rhee JH, Kim HH, Lee ZH (2008) Stimulation by TLR5 modulates osteoclast differentiation through STAT1/IFN-β. J Immunol 180:1382–1389CrossRefPubMed

Haneji T (2005) Association of protein phosphatase 1 delta with nucleolin in osteoblastic cells and cleavage of nucleolin in apoptosis-induced cells. Acta Histochem Cytochem 38:1–8CrossRef

Haneji T, Teramachi J, Hirashima K, Kimura K, Morimoto H (2012) Interaction of protein phosphatase 1δ with nucleophosmin in human osteoblastic cells. Acta Histochem Cytochem 45:1–7CrossRefPubMed

Haneji T, Hirashima K, Teramachi J, Morimoto H (2013) Okadaic acid activates PKR pathway and induces apoptosis through PKR-stimulation in osteoblastic MG63 cells. Int J Oncol 42:1904–1910PubMedPubMedCentral

Jammi NV, Beal PA (2001) Phosphorylation of the RNA-dependent protein kinase regulates its RNA-binding activity. Nucleic Acids Res 14:3020–3029CrossRef

Kito S, Shimizu K, Okamura H, Yoshida K, Fujita M, Morimoto H, Morimoto Y, Ohba T, Haneji T (2003) Cleavage of nucleolin and argyrophilic nucleolar organizer region associated proteins in apoptosis-induced cells. Biochem Biophys Res Commun 300:950–956CrossRefPubMed

Kleppe R, Herfindal L, Døskeland SO (2015) Cell death inducing microbial protein phosphatase inhibitors—mechanisms of action. Mar Drugs 13:6505–6520CrossRefPubMedPubMedCentral

Kobayashi Y, Uehara S, Udagawa N, Takahashi N (2016) Regulation of bone metabolism by Wnt signals. J Biochem 159:387–392CrossRefPubMed

Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89:755–764CrossRefPubMed

Koromilas AE (2015) Roles of the translation initiation factor eIF2α serine 51 phosphorylation in cancer formation and treatment. Biochim Biophys Acta 1849:871–880CrossRefPubMed

Lee SK, Chung JH, Choi SC, Auh QS, Lee YM, Lee SI, Kim EC (2013) Sodium hydrogen sulfide inhibits nicotine and lipopolysaccharide-induced osteoclastic differentiation and reversed osteoblastic differentiation in human periodontal ligament cells. J Cell Biochem 114:1183–1193CrossRefPubMed

L’Hote CG, Knowles MA (2005) Cell responses to FGFR3 signalling: growth, differentiation and apoptosis. Exp Cell Res 304:417–431CrossRefPubMed

Liu X, Bennett RL, Cheng X, Byrne M, Reinhard MK, May WS Jr (2013) PKR regulates proliferation, differentiation, and survival of murine hematopoietic stem/progenitor cells. Blood 121:64–74CrossRef

Lü P, Li X, Ruan L, Xu H, Liu Q (2014) Effect of siRNA PERK on fluoride-induced osteoblastic differentiation in OS732 cells. Biol Trace Elem Res 159:434–439CrossRefPubMed

Marchal JA, Lopez GJ, Peran M, Comino A, Delgado JR, García-García JA, Conde V, Aranda FM, Rivas C, Esteban M, Garcia MA (2014) The impact of PKR activation: from neurodegeneration to cancer. FASEB J 28:1965–1974CrossRefPubMed

Matsubara T, Kida K, Yamaguchi A, Hata K, Ichida F, Meguro H, Aburatani H, Nishimura R, Yoneda T (2008) BMP2 regulates Osterix through Msx2 and Runx2 during osteoblast differentiation. J Biol Chem 283:29119–29125CrossRefPubMedPubMedCentral

Morimoto Y, Ohba T, Kobayashi S, Haneji T (1997) The protein phosphatase inhibitors okadaic acid and calyculin A induce apoptosis in human osteoblastic cells. Exp Cell Res 230:181–186CrossRefPubMed

Morimoto H, Morimoto Y, Ohba T, Kido H, Kobayashi S, Haneji T (1999) Inhibitors of protein synthesis and RNA synthesis protect against okadaic acid induced apoptosis in human osteosarcoma cell line MG63 cells but not in Saos-2 cells. J Bone Miner Metab 17:266–273CrossRefPubMed

Morimoto H, Okamura H, Yoshida K, Kitamura S, Haneji T (2004a) Okadaic acid induces apoptosis through double-stranded RNA-dependent protein kinase/eukaryotic initiation factor-2α pathway in human osteoblastic MG63 cells. J Biochem 136:433–438CrossRefPubMed

Morimoto H, Okamura H, Yoshida K, Kitamura S, Haneji T (2004b) Double-stranded RNA mediates selective gene silencing of protein phosphatase type 1 delta isoform in HEK-293 cells. J Enzyme Inhib Med Chem 19:327–331CrossRefPubMed

Morimoto H, Ozaki A, Okamura H, Yoshida K, Kitamura S, Haneji T (2005) Okadaic acid induces tyrosine phosphorylation of IκBα that mediated by PKR pathway in human osteoblastic MG63 cells. Mol Cell Biochem 276:211–217CrossRefPubMed

Morimoto H, Baba R, Haneji T, Doi Y (2013) Double-stranded RNA-dependent protein kinase regulates insulin-stimulated chondrogenesis in mouse clonal chondrogenic cells, ATDC-5. Cell Tissue Res 351:41–47CrossRefPubMed

Nakashima Y, Haneji T (2013) Stimulation of osteoclast formation by RANKL requires interferon regulatory factor-4 and is inhibited by simvastatin in a mouse model of bone loss. PLoS One 8:e72033CrossRefPubMedPubMedCentral

Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, de Crombrugghe B (2002) The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108:17–29CrossRefPubMed

Nallagatla SR, Toroney R, Bevilacqua PC (2011) Regulation of innate immunity through RNA structure and the protein kinase PKR. Curr Opin Struct Biol 21:119–127CrossRefPubMed

Okamura H, Yoshida K, Ochiai K, Haneji T (2011) Reduction of protein phosphatase 2A Cα enhances bone formation and osteoblast differentiation through the expression of bone-specific transcription factor Osterix. Bone 49:368–375CrossRefPubMed

Okamura H, Yang D, Yoshida K, Haneji T (2013a) Protein phosphatase 2A Cα regulates osteoblast differentiation and the expressions of bone sialoprotein and osteocalcin via Osterix transcription factor. J Cell Physiol 228:1031–1037CrossRefPubMed

Okamura H, Yang D, Yoshida K, Haneji T (2013b) Protein phosphatase 2A Cα is involved in osteoclastogenesis by regulating RANKL and OPG expression in osteoblasts. FEBS Lett 587:48–53CrossRefPubMed

Ozaki A, Morimoto H, Tanaka H, Okamura H, Yoshida K, Amorim BR, Haneji T (2006) Okadaic acid induces phosphorylation of p65NF-κB on serine 536 and activates NF-κB transcriptional activity in human osteoblastic MG63 cells. J Cell Biochem 99:1275–1284CrossRefPubMed

Pindel A, Sadler AJ (2011) The role of protein kinase R in the interferon responses. J Interferon Cytokine Res 31:59–70CrossRefPubMed

Pytel D, Majsterek I, Diehl JA (2016) Tumor progression and the different faces of the PERK kinase. Oncogene 35:1207–1215CrossRefPubMed

Rojas M, Vasconcelos G, Dever TE (2015) An eIF2α-binding motif in protein phosphatase 1 subunit GADD34 and its viral orthologs is required to promote dephosphorylation of eIF2α. Proc Natl Acad Sci USA 112:E3466–E3475CrossRefPubMedPubMedCentral

Saelens X, Kalai M, Vandenabeele P (2001) Translation inhibition in apoptosis caspase-dependent PKR activation and eIF-2α phosphorylation. J Biol Chem 276:41620–41628CrossRefPubMed

Saito A, Ochiai K, Kondo S, Tsumagari K, Murakami T, Cavener DR, Imaizumi K (2011) Endoplasmic reticulum stress response mediated by the PERK-eIF2α-ATF4 pathway is involved in osteoblast differentiation induced by BMP2. J Biol Chem 286:4809–4818CrossRefPubMed

Salzberg S, Vilchik S, Cohen S, Heller A, Kronfeld-Kinar Y (2000) Expression of a PKR dominant-negative mutant in myogenic cells interferes with the myogenic process. Exp Cell Res 254:45–54CrossRefPubMed

Sato N, Morimoto H, Baba R, Nakamata J, Doi Y, Yamaguchi K (2010) Functional expression of double-stranded RNA-dependent protein kinase in rat intestinal epithelial cells. J Cell Biochem 110:104–111PubMed

Shinohara H, Teramachi J, Okamura H, Yang D, Nagata T, Haneji T (2015) Double stranded RNA-dependent protein kinase is necessary for TNF-α-induced osteoclast formation in vitro and in vivo. J Cell Biochem 116:1957–1967CrossRefPubMed

Shogren KL, Turner RT, Yaszemski MJ, Maran A (2007) Double-stranded RNA-dependent protein kinase is involved in 2-methoxyestradiol-mediated cell death of osteosarcoma cells. J Bone Miner Res 22:29–36CrossRefPubMedPubMedCentral

Shukunami C, Ishizeki K, Atsumi T, Ohta Y, Suzuki F, Hiraki Y (1997) Cellular hypertrophy and calcification of embryonal carcinoma-derived chondrogenic cell line ATDC5 in vitro. J Bone Miner Res 12:1174–1188CrossRefPubMed

Sims NA, Vrahnas C (2014) Regulation of cortical and trabecular bone mass by communication between osteoblasts, osteocytes and osteoclasts. Arch Biochem Biophys 561:22–28CrossRefPubMed

Sinder BP, Pettit AR, McCauley LK (2015) Macrophages: their emerging roles in bone. J Bone Miner Res 30:2140–2149CrossRefPubMedPubMedCentral

Souza PP, Lerner UH (2013) The role of cytokines in inflammatory bone loss. Immunol Invest 42:555–622CrossRefPubMed

Soysa NS, Alles N (2016) Osteoclast function and bone-resorbing activity: an overview. Biochem Biophys Res Commun 476:115–120CrossRefPubMed

Sudo H, Kodama HA, Amagai Y, Yamamoto S, Kasai S (1983) In vitro differentiation and calcification in a new clonal osteogenic cell line derived from newborn mouse calvaria. J Cell Biol 96:191–198CrossRefPubMed

Szyszka R, Kudlicki W, Kramer G, Hardesty B, Galabru J, Hovanessian A (1989) A type 1 phosphoprotein phosphatase active with phosphorylated M_r = 68,000 initiation factor 2 kinase. J Biol Chem 264:3827–3831PubMed

Takada Y, Ichikawa H, Pataer A, Swisher S, Aggarwal BB (2007) Genetic deletion of PKR abrogates TNF-induced activation of IκBα kinase, JNK, Akt and cell proliferation but potentiates p44/p42 MAPK and p38 MAPK activation. Oncogene 26:1201–1212CrossRefPubMed

Tam CL, Hofbauer M, Towle CA (2007) Requirement for protein kinase R in interleukin-1α-stimulated effects in cartilage. Biochem Pharmacol 74:1636–1641CrossRefPubMedPubMedCentral

Tan SL, Tareen SU, Melville MW, Blakely CM, Katze MG (2002) The direct binding of the catalytic subunit of protein phosphatase 1 to the PKR protein kinase is necessary but not sufficient for inactivation and disruption of enzyme dimer formation. J Biol Chem 277:36109–36117CrossRefPubMed

Tan J, Zhou L, Xue P, An Y, Luo L, Zhang R, Wu G, Wang Y, Zhu H, Wang Q (2016) Tumor necrosis factor-α attenuates the osteogenic differentiation capacity of periodontal ligament stem cells by activating PERK signalling. J Periodontol 87:159–171CrossRef

Tanaka S, Nakamura K, Takahashi N, Suda T (2005) Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL–RANK signalling system. Immunol Rev 208:30–49CrossRefPubMed

Tanaka H, Yoshida K, Okamura H, Morimoto H, Nagata T, Haneji T (2007) Calyculin A induces apoptosis and stimulates phosphorylation of p65 NF-κB in human osteoblastic osteosarcoma MG63 cells. Int J Oncol 31:389–396PubMed

Teramachi J, Morimoto H, Baba R, Doi Y, Hirashima K, Haneji T (2010) Double stranded RNA-dependent protein kinase is involved in osteoclast differentiation of RAW264.7 cells in vitro. Exp Cell Res 316:3254–3262CrossRefPubMed

Teramachi J, Inagaki Y, Shinohara H, Okamura H, Yang D, Ochiai K, Baba R, Morimoto H, Nagata T, Haneji T (2016) PKR regulates LPS-induced osteoclast formation and bone destruction in vitro and in vivo. Oral Dis. doi:10.1111/odi.12592 PubMed

Wada T, Nakashima T, Nishina H, Penninger JM (2006) RANKL–RANK signalling in osteoclastogenesis and bone disease. Trends Mol Med 12:17–25CrossRefPubMed

Wakula P, Beullens M, van Eynde A, Ceulemans H, Stalmans W, Bollen M (2006) The translation initiation factor eIF2β is an interactor of protein phosphatase-1. Biochem J 400:377–383CrossRefPubMedPubMedCentral

Xu Z, Williams BR (2000) The B56α regulatory subunit of protein phosphatase 2A is a target for regulation by double-stranded RNA-dependent protein kinase PKR. Mol Cell Biol 20:5285–5299CrossRefPubMedPubMedCentral

Yang C, Shogren KL, Goyal R, Bravo D, Yaszemski MJ, Maran A (2013a) RNA-dependent protein kinase is essential for 2-methoxyestradiol-induced autophagy in osteosarcoma cells. PLoS One 8:e59406CrossRefPubMedPubMedCentral

Yang D, Okamura H, Nakashima Y, Haneji T (2013b) Histone demethylase Jmjd3 regulates osteoblast differentiation via transcription factors Runx2 and Osterix. J Biol Chem 288:33530–33541CrossRefPubMedPubMedCentral

Yang D, Okamura H, Teramachi J, Haneji T (2015) Histone demethylase Utx regulates osteoblast differentiation and mineralization. J Cell Biochem 116:2628–2636CrossRefPubMed

Yang D, Okamura H, Teramachi J, Haneji T (2016a) Histone demethylase Jmjd3 regulates osteoblast differentiation through targeting anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bim. Biochim Biophys Acta 1863:650–659CrossRefPubMed

Yang D, Okamura H, Morimoto H, Teramachi J, Haneji T (2016b) Protein phosphatase 2A Cα regulates proliferation, migration, and metastasis of osteosarcoma cells. Lab Invest 96:1050–1062CrossRefPubMed

Yim HC, Williams BR (2014) Protein kinase R and the inflammasome. J Interferon Cytokine Res 34:447–454CrossRefPubMed

Yoshida K, Okamura H, Amorim BR, Ozaki A, Tanaka H, Morimoto H, Haneji T (2005) Double-stranded RNA-dependent protein kinase is required for bone calcification in MC3T3-E1 cells in vitro. Exp Cell Res 311:117–125CrossRefPubMed

Yoshida K, Okamura H, Amorim BR, Hinode D, Yoshida H, Haneji T (2009) PKR-mediated degradation of STAT1 regulates osteoblast differentiation. Exp Cell Res 315:2105–2114CrossRefPubMed

Yoshida K, Okamura H, Ochiai K, Hoshino Y, Haneji T, Yoshioka M, Hinode D, Yoshida H (2012) PKR plays a positive role in osteoblast differentiation by regulating GSK-3β activity through β-catenin-independent pathway. Mol Cell Endocrinol 361:99–105CrossRefPubMed

Titel: Roles of PKR in differentiation and apoptosis of bone-related cells
verfasst von: Tatsuji Haneji
Publikationsdatum: 16.12.2016
Verlag: Springer Japan
Erschienen in: Anatomical Science International / Ausgabe 3/2017
Print ISSN: 1447-6959
Elektronische ISSN: 1447-073X
DOI: https://doi.org/10.1007/s12565-016-0385-3

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