Abstract
Heat shock proteins (HSPs) are a family of proteins produced by cells in response to exposure to stressful conditions. In addition to their role as chaperones, they also play an important role in the cardiovascular, immune, and other systems. Normal bone tissue is maintained by bone metabolism, particularly by the balance between osteoblasts and osteoclasts, which are physiologically regulated by multiple hormones and cytokines. In recent years, studies have reported the vital role of HSPs in bone metabolism. However, the conclusions remain largely controversial, and the exact mechanisms are still unclear, so a review and analyses of previous studies are of importance. This article reviews the current understanding of the roles and effects of HSPs on bone cells (osteoblasts, osteoclasts, and osteocytes), in relation to bone metabolism.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Antonova G, Lichtenbeld H, Xia T, Chatterjee A, Dimitropoulou C, Catravas JD (2007) Functional significance of hsp90 complexes with NOS and sGC in endothelial cells. Clin Hemorheol Microcirc 37(1–2):19–35
Bakthisaran R, Tangirala R, Rao Ch M (2015) Small heat shock proteins: role in cellular functions and pathology. Biochim Biophys Acta 1854(4):291–319. https://doi.org/10.1016/j.bbapap.2014.12.019
Barazi HO, Zhou L, Templeton NS, Krutzsch HC, Roberts DD (2002) Identification of heat shock protein 60 as a molecular mediator of alpha 3 beta 1 integrin activation. Cancer Res 62(5):1541–1548
Beere HM, Wolf BB, Cain K, Mosser DD, Mahboubi A, Kuwana T, Tailor P, Morimoto RI, Cohen GM, Green DR (2000) Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol 2(8):469–75.10.1038/35019501
Boskey AL, Wians FH Jr, Hauschka PV (1985) The effect of osteocalcin on in vitro lipid-induced hydroxyapatite formation and seeded hydroxyapatite growth. Calcif Tissue Int 37(1):57–62
Cao Y, Ohwatari N, Matsumoto T, Kosaka M, Ohtsuru A, Yamashita S (1999) TGF-beta1 mediates 70-kDa heat shock protein induction due to ultraviolet irradiation in human skin fibroblasts. Pflugers Arch 438(3):239–244
Cappello F et al (2006) Hsp60 and Hsp10 down-regulation predicts bronchial epithelial carcinogenesis in smokers with chronic obstructive pulmonary disease. Cancer 107(10):2417–2424. https://doi.org/10.1002/cncr.22265
Cappello F, Conway de Macario E, Marasà L, Zummo G, Macario AJL (2008) Hsp60 expression, new locations, functions and perspectives for cancer diagnosis and therapy. Cancer Biol Ther 7(6):801–809
Capulli M, Paone R, Rucci N (2014) Osteoblast and osteocyte: games without frontiers. Arch Biochem Biophys 561:3–12. https://doi.org/10.1016/j.abb.2014.05.003
Chai RC et al (2014) Molecular stress-inducing compounds increase osteoclast formation in a heat shock factor 1 protein-dependent manner. J Biol Chem 289(19):13602–13614. https://doi.org/10.1074/jbc.M113.530626
Chen W et al (1999) Human 60-kDa heat-shock protein: a danger signal to the innate immune system. J Immunol 162(6):3212–3219
Chen Y et al (2013) Targeting HSF1 sensitizes cancer cells to HSP90 inhibition. Oncotarget 4(6):816–829. https://doi.org/10.18632/oncotarget.991
Chen E et al (2015) Extracellular heat shock protein 70 promotes osteogenesis of human mesenchymal stem cells through activation of the ERK signaling pathway. FEBS Lett 589(24 Pt B):4088–4096. https://doi.org/10.1016/j.febslet.2015.11.021
Chen H et al (2017) Inhibition of heat shock protein 90 rescues glucocorticoid-induced bone loss through enhancing bone formation. J Steroid Biochem Mol Biol 171:236–246. https://doi.org/10.1016/j.jsbmb.2017.04.004
Ciocca DR, Cayado-Gutierrez N, Maccioni M, Cuello-Carrion FD (2012) Heat shock proteins (HSPs) based anti-cancer vaccines. Curr Mol Med 12(9):1183–1197
Cooper LF, Uoshima K (1994) Differential estrogenic regulation of small M(r) heat shock protein expression in osteoblasts. J Biol Chem 269(11):7869–7873
Dallas SL, Bonewald LF (2010) Dynamics of the transition from osteoblast to osteocyte. Ann N Y Acad Sci 1192:437–443. https://doi.org/10.1111/j.1749-6632.2009.05246.x
Didelot C, Lanneau D, Brunet M, Joly AL, Thonel A, Chiosis G, Garrido C (2007) Anti-cancer therapeutic approaches based on intracellular and extracellular heat shock proteins. Curr Med Chem 14(27):2839–2847
Ducy P et al (1996) Increased bone formation in osteocalcin-deficient mice. Nature 382(6590):448–452. https://doi.org/10.1038/382448a0
Etienne S, Gaborit N, Henrionnet C, Pinzano A, Galois L, Netter P, Gillet P, Grossin L (2008) Local induction of heat shock protein 70 (Hsp70) by proteasome inhibition confers chondroprotection during surgically induced osteoarthritis in the rat knee. Biomed Mater Eng 18(4–5):253–260
Flanagan M et al (2017) Downregulation of heat shock protein B8 decreases osteogenic differentiation potential of dental pulp stem cells during in vitro proliferation. Cell Prolif. https://doi.org/10.1111/cpr.12420
Francis LK et al (2006) Combination mammalian target of rapamycin inhibitor rapamycin and HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin has synergistic activity in multiple myeloma. Clin Cancer Res 12(22):6826–6835. https://doi.org/10.1158/1078-0432.ccr-06-1331
Fujita S et al (2012) Combined microwave irradiation and intraarticular glutamine administration-induced HSP70 expression therapy prevents cartilage degradation in a rat osteoarthritis model. J Orthop Res 30(3):401–407. https://doi.org/10.1002/jor.21535
Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N (1999) VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 5(6):623–628. https://doi.org/10.1038/9467
Grossin L et al (2006) Gene transfer with HSP 70 in rat chondrocytes confers cytoprotection in vitro and during experimental osteoarthritis. Faseb J 20(1):65–75. https://doi.org/10.1096/fj.04-2889com
Hatakeyama D, Kozawa O, Niwa M, Matsuno H, Ito H, Kato K, Tatematsu N, Shibata T, Uematsu T (2002) Upregulation by retinoic acid of transforming growth factor-beta-stimulated heat shock protein 27 induction in osteoblasts: involvement of mitogen-activated protein kinases. Biochim Biophys Acta 1589(1):15–30
Hoang QQ et al (2003) Bone recognition mechanism of porcine osteocalcin from crystal structure. Nature 425(6961):977–980. https://doi.org/10.1038/nature02079
Hunter GK et al (1996) Nucleation and inhibition of hydroxyapatite formation by mineralized tissue proteins. Biochem J 317(Pt 1):59–64
Jindal S, Dudani AK, Singh B, Harley CB, Gupta RS (1989) Primary structure of a human mitochondrial protein homologous to the bacterial and plant chaperonins and to the 65-kilodalton mycobacterial antigen. Mol Cell Biol 9(5):2279–2283
Julio CB, Carlos HIR (2005) Protein folding assisted by chaperones. Protein Pept Lett 12(3):257–261. https://doi.org/10.2174/0929866053587165
Kainuma S et al (2017) Heat shock protein 27 (HSPB1) suppresses the PDGF-BB-induced migration of osteoblasts. Int J Mol Med 40(4):1057–1066. https://doi.org/10.3892/ijmm.2017.3119
Kampinga HH et al (2009) Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones 14(1):105–111. https://doi.org/10.1007/s12192-008-0068-7
Kato K et al (2010) Rho-kinase regulates prostaglandin D(2)-stimulated heat shock protein 27 induction in osteoblasts. Exp Ther Med 1(4):579–583. https://doi.org/10.3892/etm_00000091
Kato K et al (2011a) Role of heat shock protein 27 in transforming growth factor-beta-stimulated vascular endothelial growth factor release in osteoblasts. Int J Mol Med 27(3):423–428. https://doi.org/10.3892/ijmm.2011.595
Kato K et al (2011b) Regulation by heat shock protein 27 of osteocalcin synthesis in osteoblasts. Endocrinology 152(5):1872–1882. https://doi.org/10.1210/en.2010-1062
Kawamura H et al (1999) Endothelin-1 stimulates heat shock protein 27 induction in osteoblasts: involvement of p38 MAP kinase. Am J Phys 277(6 Pt 1):E1046–E1054
Kim YS et al (2009) Increased circulating heat shock protein 60 induced by menopause, stimulates apoptosis of osteoblast-lineage cells via up-regulation of toll-like receptors. Bone 45(1):68–76. https://doi.org/10.1016/j.bone.2009.03.658
Kirby AC et al (1995) The potent bone-resorbing mediator of Actinobacillus actinomycetemcomitans is homologous to the molecular chaperone GroEL. J Clin Invest 96(3):1185–1194. https://doi.org/10.1172/jci118150
Koh JM et al (2009) Heat shock protein 60 causes osteoclastic bone resorption via toll-like receptor-2 in estrogen deficiency. Bone 45(4):650–660. https://doi.org/10.1016/j.bone.2009.06.007
Kondo A et al (2013) Unphosphorylated heat shock protein 27 suppresses fibroblast growth factor2stimulated vascular endothelial growth factor release in osteoblasts. Mol Med Rep 8(2):691–695. https://doi.org/10.3892/mmr.2013.1533
Kousteni S et al (2002) Reversal of bone loss in mice by nongenotropic signaling of sex steroids. Science 298(5594):843–846. https://doi.org/10.1126/science.1074935
Kozawa O, Tokuda H (2002) Heat shock protein 27 in osteoblasts. Nihon Yakurigaku Zasshi 119(2):89–94
Kozawa O et al (1999a) Sphingosine 1-phosphate induces heat shock protein 27 via p38 mitogen-activated protein kinase activation in osteoblasts. J Bone Miner Res 14(10):1761–1767. https://doi.org/10.1359/jbmr.1999.14.10.1761
Kozawa O, Tokuda H, Miwa M, Ito H, Matsuno H, Niwa M, Kato K, Uematsu T (1999b) Involvement of p42/p44 mitogen-activated protein kinase in prostaglandin f(2alpha)-stimulated induction of heat shock protein 27 in osteoblasts. J Cell Biochem 75(4):610–619
Kozawa O et al (2001a) Stimulatory effect of basic fibroblast growth factor on induction of heat shock protein 27 in osteoblasts: role of protein kinase C. Arch Biochem Biophys 388(2):237–242. https://doi.org/10.1006/abbi.2000.2290
Kozawa O, Otsuka T, Hatakeyama D, Niwa M, Matsuno H, Ito H, Kato K, Matsui N, Uematsu T (2001b) Mechanism of prostaglandin D(2)-stimulated heat shock protein 27 induction in osteoblasts. Cell Signal 13(8):535–541
Kozawa O et al (2002) Specific induction of heat shock protein 27 by glucocorticoid in osteoblasts. J Cell Biochem 86(2):357–364. https://doi.org/10.1002/jcb.10221
Laplante AF, Moulin V, Auger FA, Landry J, Li H, Morrow G, Tanguay RM, Germain L (1998) Expression of heat shock proteins in mouse skin during wound healing. Journal of Histochemistry & Cytochemistry 46(11):1291–1301.10.1177/002215549804601109
Leonardi R et al (2004) Immunolocalization of heat shock protein 27 in developing jaw bones and tooth germs of human fetuses. Calcif Tissue Int 75(6):509–516. https://doi.org/10.1007/s00223-004-0077-1
Li C et al (2018) Downregulation of heat shock protein 70 impairs osteogenic and chondrogenic differentiation in human mesenchymal stem cells. Sci Rep 8(1):553. https://doi.org/10.1038/s41598-017-18541-1
Loones MT, Morange M (1998) Hsp and chaperone distribution during endochondral bone development in mouse embryo. Cell Stress Chaperones 3(4):237–244
Lu MC et al (2016) Anti-citrullinated protein antibodies promote apoptosis of mature human Saos-2 osteoblasts via cell-surface binding to citrullinated heat shock protein 60. Immunobiology 221(1):76–83. https://doi.org/10.1016/j.imbio.2015.07.019
Lurje G, Lenz HJ (2009) EGFR signaling and drug discovery. Oncology 77(6):400–10.10.1159/000279388
Makareeva E, Aviles NA, Leikin S (2011) Chaperoning osteogenesis: new protein-folding-disease paradigms. Trends Cell Biology 21(3):168–176. https://doi.org/10.1016/j.tcb.2010.11.007
Manolagas SC et al (2000) Endocr Rev 21(2):115–137. https://doi.org/10.1210/edrv.21.2.0395
Mashaghi A et al (2016) Alternative modes of client binding enable functional plasticity of Hsp70. Nature 539(7629):448–451. https://doi.org/10.1038/nature20137
Matz JM et al (1995) Characterization and regulation of cold-induced heat shock protein expression in mouse brown adipose tissue. Am J Physiol 269(1 Pt 2):R38–R47. https://doi.org/10.1152/ajpregu.1995.269.1.R38
Meghji S, Lillicrap M, Maguire M, Tabona P, Gaston JSH, Poole S, Henderson B (2003) Human chaperonin 60 (Hsp60) stimulates bone resorption: structure/function relationships. Bone 33(3):419–425
Menanteau J, Neuman WF, Neuman MW (1982) A study of bone proteins which can prevent hydroxyapatite formation. Metab Bone Dis Relat Res 4(2):157–162
Miyasaka M et al (2016) Low-intensity pulsed ultrasound stimulation enhances heat-shock protein 90 and mineralized nodule formation in mouse calvaria-derived osteoblasts. Tissue Eng Part A 22(9–10):827–828. https://doi.org/10.1089/ten.tea.2015.0234.correx Correction Re: Tissue engineering, Part A, 2015;21(23–24):2829–2839
Morii T, Ohtsuka K, Ohnishi H, Mochizuki K, Satomi K (2010) Inhibition of heat-shock protein 27 expression eliminates drug resistance of osteosarcoma to zoledronic acid. Anticancer Res 30(9):3565–3571
Morimoto RI (1993) Cells in stress: transcriptional activation of heat shock genes. Science 259(5100):1409–1410
Nakashima T (2015) Bone and Calcium Research Update 2015. Regulation of bone remodeling by osteocytes. Clin Calcium 25(1):21–8.CliCa15012128
Nakashima T, Hayash M, Takayanagi H (2012) Regulation of bone resorption by osteocytes. Clin Calcium 22(5):685–96.CliCa1205685696
Natsume H et al (2009) Involvement of Rho-kinase in TGF-beta-stimulated heat shock protein 27 induction in osteoblasts. Mol Med Rep 2(5):687–691. https://doi.org/10.3892/mmr_00000157
Neve A, Corrado A, Cantatore FP (2013) Osteocalcin: skeletal and extra-skeletal effects. J Cell Physiol 228(6):1149–1153. https://doi.org/10.1002/jcp.24278
Nishikawa M, Takemoto S, Takakura Y (2008) Heat shock protein derivatives for delivery of antigens to antigen presenting cells. Int J Pharm 354(1–2):23–27. https://doi.org/10.1016/j.ijpharm.2007.09.030
Notsu K, Nakagawa M, Nakamura M (2016) Ubiquitin-like protein MNSFbeta noncovalently binds to molecular chaperone HSPA8 and regulates osteoclastogenesis. Mol Cell Biochem 421(1–2):149–156. https://doi.org/10.1007/s11010-016-2795-x
Ohashi K et al (2000) Cutting edge: heat shock protein 60 is a putative endogenous ligand of the Toll-like receptor-4 complex. J Immunol 164(2):558–561. https://doi.org/10.4049/jimmunol.164.2.558
Okawa Y et al (2009) SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematologic tumors by abrogating signaling via Akt and ERK. Blood 113(4):846–855. https://doi.org/10.1182/blood-2008-04-151928
Price JT et al (2005) The heat shock protein 90 inhibitor, 17-allylamino-17-demethoxygeldanamycin, enhances osteoclast formation and potentiates bone metastasis of a human breast cancer cell line. Cancer Res 65(11):4929–4938. https://doi.org/10.1158/0008-5472.can-04-4458
Quintana FJ, Cohen IR (2011) The HSP60 immune system network. Trends Immunol 32(2):89–95. https://doi.org/10.1016/j.it.2010.11.001
Raggatt LJ, Partridge NC (2010) Cellular and molecular mechanisms of bone remodeling. J Biol Chem 285(33):25103–25108. https://doi.org/10.1074/jbc.R109.041087
Rammelt S et al (2005) Osteocalcin enhances bone remodeling around hydroxyapatite/collagen composites. J Biomed Mater Res A 73(3):284–294. https://doi.org/10.1002/jbm.a.30263
Ranford JC, Henderson B (2002) Chaperonins in disease: mechanisms, models, and treatments. Mol Pathol 55(4):209–213
Ranford JC, Coates AR, Henderson B (2000) Chaperonins are cell-signalling proteins: the unfolding biology of molecular chaperones. Expert Rev Mol Med 2(8):1–17. https://doi.org/10.1017/S1462399400002015
Reddi K et al (1998) The Escherichia coli chaperonin 60 (groEL) is a potent stimulator of osteoclast formation. J Bone Miner Res 13(8):1260–1266. https://doi.org/10.1359/jbmr.1998.13.8.1260
Ritossa F (1962) A new puffing pattern induced by temperature shock and DNP in drosophila. Experientia 18(12):571–573. https://doi.org/10.1007/bf02172188
Romberg RW, Werness PG, Riggs BL, Mann KG (1986) Inhibition of hydroxyapatite crystal growth by bone-specific and other calcium-binding proteins. Biochemistry 25(5):1176–1180
Sakai G, Tokuda H, Fujita K, Kainuma S, Kawabata T, Matsushima-Nishiwaki R, Kozawa O, Otsuka T (2017) Heat shock protein 70 negatively regulates TGF-beta-stimulated VEGF synthesis via p38 MAP kinase in osteoblasts. Cell Physiol Biochem 44(3):1133–1145.10.1159/000485418
Sarto C, Binz PA, Mocarelli P (2000) Heat shock proteins in human cancer. ELECTROPHORESIS 21(6):1218–1226. https://doi.org/10.1002/(SICI)1522-2683(20000401)21:6<1218::AID-ELPS1218>3.0.CO;2-H
Sawai A et al (2008) Inhibition of Hsp90 down-regulates mutant epidermal growth factor receptor (EGFR) expression and sensitizes EGFR mutant tumors to paclitaxel. Cancer Res 68(2):589–596. https://doi.org/10.1158/0008-5472.can-07-1570
Schlesinger MJ (1990) Heat shock proteins. J Biol Chem 265(21):12111–12114
Shakoori AR et al (1992) Expression of heat shock genes during differentiation of mammalian osteoblasts and promyelocytic leukemia cells. J Cell Biochem 48(3):277–287. https://doi.org/10.1002/jcb.240480308
Siebelt M et al (2013) Hsp90 inhibition protects against biomechanically induced osteoarthritis in rats. Arthritis Rheum 65(8):2102–2112. https://doi.org/10.1002/art.38000
Sims NA and Martin TJ (2014) Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit. BoneKEy Rep 3. https://doi.org/10.1038/bonekey.2013.215
Soltys BJ, Gupta RS (1997) Cell surface localization of the 60 kDa heat shock chaperonin protein (hsp60) in mammalian cells. Cell Biol Int 21(5):315–320. https://doi.org/10.1006/cbir.1997.0144
Sorger PK (1991) Heat shock factor and the heat shock response. Cell 65(3):363–366. https://doi.org/10.1016/0092-8674(91)90452-5
Suzuki A et al (1996) Protein kinase C activation inhibits stress-induced synthesis of heat shock protein 27 in osteoblast-like cells: function of arachidonic acid. J Cell Biochem 62(1):69–75. https://doi.org/10.1002/(SICI)1097-4644(199607)62:1<69::AID-JCB8>3.0.CO;2-#
Tavaria M, Gabriele T, Kola I, Anderson RL (1996) A hitchhiker’s guide to the human Hsp70 family. Cell Stress Chaperones 1(1):23–28
Taylor RP, Benjamin IJ (2005) Small heat shock proteins: a new classification scheme in mammals. J Mol Cell Cardiol 38(3):433–444. https://doi.org/10.1016/j.yjmcc.2004.12.014
Tokuda H, Kozawa O, Niwa M, Matsuno H, Kato K, Uematsu T (2002) Mechanism of prostaglandin E2-stimulated heat shock protein 27 induction in osteoblast-like MC3T3-E1 cells. J Endocrinol 172(2):271–281
Tokuda H, Niwa M, Ito H, Oiso Y, Kato K, Kozawa O (2003) Involvement of stress-activated protein kinase/c-Jun N-terminal kinase in endothelin-1-induced heat shock protein 27 in osteoblasts. Eur J Endocrinol 149(3):239–245
Tokuda H et al (2004) Involvement of stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) in prostaglandin F2alpha-induced heat shock protein 27 in osteoblasts. Prostaglandins Leukot Essent Fat Acids 70(5):441–447. https://doi.org/10.1016/j.plefa.2003.09.006
Trieb K, Lechleitner T, Lang S, Windhager R, Kotz R, Dirnhofer S (1998) Heat shock protein 72 expression in osteosarcomas correlates with good response to neoadjuvant chemotherapy. Hum Pathol 29(10):1050–1055
Trieb K, Lang S, Kotz R (2000a) Heat-shock protein 72 in human osteosarcoma: T-lymphocyte reactivity and cytotoxicity. Pediatr Hematol Oncol 17(5):355–364. https://doi.org/10.1080/08880010050034283
Trieb K et al (2000b) Antibodies to heat shock protein 90 in osteosarcoma patients correlate with response to neoadjuvant chemotherapy. Br J Cancer 82(1):85–87. https://doi.org/10.1054/bjoc.1999.0881
Trieb K et al (2000c) Serum antibodies against the heat shock protein 60 are elevated in patients with osteosarcoma. Immunobiology 201(3–4):368–376. https://doi.org/10.1016/s0171-2985(00)80091-1
Urushibara M et al (2007) HSP60 may predict good pathological response to neoadjuvant chemoradiotherapy in bladder cancer. Jpn J Clin Oncol 37(1):56–61. https://doi.org/10.1093/jjco/hyl121
Vabulas RM et al (2001) Endocytosed HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells. J Biol Chem 276(33):31332–31339. https://doi.org/10.1074/jbc.M103217200
van der Kraan AG et al (2013) HSP90 inhibitors enhance differentiation and MITF (microphthalmia transcription factor) activity in osteoclast progenitors. Biochem J 451(2):235–244. https://doi.org/10.1042/bj20121626
Vargas-Roig LM, Fanelli MA, López LA, Gago FE, Tello O, Aznar JC, Ciocca DR (1997) Heat shock proteins and cell proliferation in human breast cancer biopsy samples. Cancer Detect Prev 21(5):441–451
Vilaboa N et al (2017) New inhibitor targeting human transcription factor HSF1: effects on the heat shock response and tumor cell survival. Nucleic Acids Res 45(10):5797–5817. https://doi.org/10.1093/nar/gkx194
Wada T et al (2006) RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med 12(1):17–25. https://doi.org/10.1016/j.molmed.2005.11.007
Walter S, Buchner J (2002) Molecular chaperones—cellular machines for protein folding. Angew Chem Int Ed Engl 41(7):1098–1113
Watanabe S et al (2003) IgG and IgA antibody titers against human heat-shock protein (hsp60) in sera of rheumatoid arthritis and osteoarthritis patients. Mod Rheumatol 13(1):22–26. https://doi.org/10.3109/s101650300003
Winrow VR et al (2008) The two homologous chaperonin 60 proteins of Mycobacterium tuberculosis have distinct effects on monocyte differentiation into osteoclasts. Cell Microbiol 10(10):2091–2104. https://doi.org/10.1111/j.1462-5822.2008.01193.x
Woodlock TJ et al (1997) Association of HSP60-like proteins with the L-system amino acid transporter. Arch Biochem Biophys 338(1):50–56. https://doi.org/10.1006/abbi.1996.9798
Wyzewski Z et al (2018) Functional role of Hsp60 as a positive regulator of human viral infection progression. Acta Virol 62(1):33–40. https://doi.org/10.4149/av_2018_104
Xu Q et al (1994) Surface staining and cytotoxic activity of heat-shock protein 60 antibody in stressed aortic endothelial cells. Circ Res 75(6):1078–1085. https://doi.org/10.1161/01.res.75.6.1078
Yamamoto N et al (2016) Heat shock protein 22 (HSPB8) limits TGF-beta-stimulated migration of osteoblasts. Mol Cell Endocrinol 436:1–9. https://doi.org/10.1016/j.mce.2016.07.011
Yano A et al (2008) Inhibition of Hsp90 activates osteoclast c-Src signaling and promotes growth of prostate carcinoma cells in bone. Proc Natl Acad Sci U S A 105(40):15541–15546. https://doi.org/10.1073/pnas.0805354105
Yoshida M et al (2004) Methotrexate enhances prostaglandin D2-stimulated heat shock protein 27 induction in osteoblasts. Prostaglandins Leukot Essent Fat Acids 71(6):351–362. https://doi.org/10.1016/j.plefa.2004.06.003
Zhang W et al (2016) Overexpression of HSPA1A enhances the osteogenic differentiation of bone marrow mesenchymal stem cells via activation of the Wnt/beta-catenin signaling pathway. Sci Rep 6:27622. https://doi.org/10.1038/srep27622
Funding
This work was supported by grants from the National Natural Science Foundation of China (nos. 81672147, 81401011, 81201397, and 81271973); Zhejiang Provincial Natural Science Foundation of China (nos. LY15H060001, LY15H060002, and LY16H060003); the Education Department of Zhejiang Province (nos. Y201328201 and Y201534637); Public welfare projects of Zhejiang Science and Technology Department (no. 2012C23079); and Zhejiang medical and health science and technology plan project (nos. 2015KYB182, 2017KY382, 2015104766, and 2014KYA092).
Author information
Authors and Affiliations
Contributions
ZJP and DTX: conception and design; KH, CY, and EC: literature research and review. WZ: data collecting; KH, CY, and EC: article writing with contributions from other authors.
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Rights and permissions
About this article
Cite this article
Hang, K., Ye, C., Chen, E. et al. Role of the heat shock protein family in bone metabolism. Cell Stress and Chaperones 23, 1153–1164 (2018). https://doi.org/10.1007/s12192-018-0932-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12192-018-0932-z