Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
BMC Oral Health
Published in: BMC Oral Health 1/2018

Open Access 01-12-2018 | Research article

HDAC6 regulates dental mesenchymal stem cells and osteoclast differentiation

Authors: Yi Wang, Zhi Yun Shi, Jin Feng, Jun Kai Cao

Published in: BMC Oral Health | Issue 1/2018

Login to get access

Abstract

Background

Dental and periodontal tissue development is a complicated process involving a finely regulated network of communication among various cell types. Understanding the mechanisms involved in regulating dental mesenchymal stem cells (MSCs) and osteoclast cell differentiation is critical. However, it is still unclear whether histone deacetylase HDAC6 is involved in dental MSCs fate determination and osteoclast differentiation.

Methods

We used shRNA and siRNA knockdown to explore the role of HDAC6 in dental MSCs odontogenic differentiation and osteoclasts maturation.

Results

Based on HDAC6 knockdown dental MSCs, our data suggest that HDAC6 knockdown significantly increases alkaline phosphate activity and mineralized nodules formation. Additionally, mRNA expression of odontogenic marker genes (OSX, OCN, and OPN) was induced by HDAC6 knockdown. By using HDAC6 siRNA, we knocked down HDAC6 in osteoclast precursor RAW 264.7 cells. Our data suggests that HDAC6 knockdown significantly inhibited osteoclasts differentiation. Additionally, mRNA expression of osteoclast marker genes Trap, Mmp9, and Ctsk was decreased by HDAC6 knockdown.

Conclusions

Our study demonstrated that HDAC6 plays an important role in regulating dental MSCs and osteoclasts differentiation.
Literature
1.
Undale AH, Westendorf JJ, Yaszemski MJ, Khosla S. Mesenchymal stem cells for bone repair and metabolic bone diseases. Mayo Clin Proc. 2009;84:893–902.CrossRef
2.
Hoffmuller U. MSC 2007--Adult Mesenchymal Stem Cells in Regenerative Medicine. Developments in stem cell therapeutic research. IDrugs. 2007;10(11):787–90.
3.
Kaiser S, Hackanson B, Follo M, Mehlhorn A, Geiger K, et al. BM cells giving rise to MSC in culture have a heterogeneous CD34 and CD45 phenotype. Cytotherapy. 2007;9:439–50.CrossRef
4.
Kukita T, Kukita A, Iijima T. Osteoclast differentiation antigen involved the induction of calcitonin escape phenomenon. Kaibogaku Zasshi. 2000;75:433–8.PubMed
5.
Shalhoub V, Elliott G, Chiu L, Manoukian R, Kelley M, et al. Characterization of osteoclast precursors in human blood. Br J Haematol. 2000;111:501–12.CrossRef
6.
Cantley MD, Zannettino ACW, Bartold PM, Fairlie DP, Haynes DR. Histone deacetylases (HDAC) in physiological and pathological bone remodelling. Bone. 2017;95:162–74.CrossRef
7.
Schroeder TM, Westendorf JJ. Histone deacetylase inhibitors promote osteoblast maturation. J Bone Miner Res. 2005;20:2254–63.CrossRef
8.
Nakamura T, Kukita T, Shobuike T, Nagata K, Wu Z, et al. Inhibition of histone deacetylase suppresses osteoclastogenesis and bone destruction by inducing IFN-beta production. J Immunol. 2005;175:5809–16.CrossRef
9.
Holt RD, Oliver M. Evaluating web-based learning modules during an MSc programme in dental public health: a case study. Br Dent J. 2002;193:283–6.CrossRef
10.
Calvert G, Britten N. The united medical and dental School of Guy's and St Thomas' Hospitals' MSc in general practice: graduates' perspectives. Med Educ. 1999;33:130–5.CrossRef
11.
Smith GP. Formula for success: the role of the MSC officer and the U.S. Army dental care system. Mil Med. 1991;156:134–6.CrossRef
12.
Lian JB, Javed A, Zaidi SK, Lengner C, Montecino M, et al. Regulatory controls for osteoblast growth and differentiation: role of Runx/Cbfa/AML factors. Crit Rev Eukaryot Gene Expr. 2004;14:1–41.CrossRef
13.
Gharibi B, Ghuman MS, Hughes FJ. Akt- and Erk-mediated regulation proliferation and differentiation during PDGFRbeta-induced MSC self-renewal. J Cell Mol Med. 2012;16:2789–801.CrossRef
14.
Roche S, Richard MJ, Favrot MC. Oct-4, rex-1, and Gata-4 expression in human MSC increase the differentiation efficiency but not hTERT expression. J Cell Biochem. 2007;101:271–80.CrossRef
15.
Srivastava S, Toraldo G, Weitzmann MN, Cenci S, Ross FP, et al. Estrogen decreases osteoclast formation by down-regulating receptor activator of NF-kappa B ligand (RANKL)-induced JNK activation. J Biol Chem. 2001;276:8836–40.CrossRef
16.
Neale SD, Smith R, Wass JA, Athanasou NA. Osteoclast differentiation from circulating mononuclear precursors in Paget's disease is hypersensitive to 1,25-dihydroxyvitamin D(3) and RANKL. Bone. 2000;27:409–16.CrossRef
17.
Kobayashi K, Takahashi N, Jimi E, Udagawa N, Takami M, et al. Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med. 2000;191:275–86.CrossRef
18.
Karamboulas C, Swedani A, Ward C, Al-Madhoun AS, Wilton S, et al. HDAC activity regulates entry of mesoderm cells into the cardiac muscle lineage. J Cell Sci. 2006;119:4305–14.CrossRef
19.
Takahashi-Fujigasaki J, Fujigasaki H. Histone deacetylase (HDAC) 4 involvement in both Lewy and Marinesco bodies. Neuropathol Appl Neurobiol. 2006;32:562–6.CrossRef
20.
Santo L, Hideshima T, Kung AL, Tseng JC, Tamang D, et al. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood. 2012;119:2579–89.CrossRef
21.
Bobrowska A, Paganetti P, Matthias P, Bates GP. Hdac6 knock-out increases tubulin acetylation but does not modify disease progression in the R6/2 mouse model of Huntington's disease. PLoS One. 2011;6:e20696.CrossRef
22.
Destaing O, Saltel F, Gilquin B, Chabadel A, Khochbin S, et al. A novel rho-mDia2-HDAC6 pathway controls podosome patterning through microtubule acetylation in osteoclasts. J Cell Sci. 2005;118:2901–11.CrossRef
23.
Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A. 2000;97:13625–30.CrossRef
24.
Sun SZ, Liu SH, Wei FC, Zhang CY, Liu YS. The ALP activity of cultured dental coronal and root pulp cells in vitro. Shanghai Kou Qiang Yi Xue. 2004;13:531.PubMed
25.
Lindunger A, MacKay CA, Ek-Rylander B, Andersson G, Marks SC Jr. Histochemistry and biochemistry of tartrate-resistant acid phosphatase (TRAP) and tartrate-resistant acid adenosine triphosphatase (TrATPase) in bone, bone marrow and spleen: implications for osteoclast ontogeny. Bone Miner. 1990;10:109–19.CrossRef
26.
Kusano K, Miyaura C, Inada M, Tamura T, Ito A, et al. Regulation of matrix metalloproteinases (MMP-2, −3, −9, and −13) by interleukin-1 and interleukin-6 in mouse calvaria: association of MMP induction with bone resorption. Endocrinology. 1998;139:1338–45.CrossRef
27.
Choi J, Choi SY, Lee SY, Lee JY, Kim HS, et al. Caffeine enhances osteoclast differentiation and maturation through p38 MAP kinase/Mitf and DC- STAMP/CtsK and TRAP pathway. Cell Signal. 2013;25:1222–7.CrossRef
28.
Ravindran S, Huang CC, George A. Extracellular matrix of dental pulp stem cells: applications in pulp tissue engineering using somatic MSCs. Front Physiol. 2014;4:395.CrossRef
29.
Jewett A, Arasteh A, Tseng HC, Behel A, Arasteh H, et al. Strategies torescue mesenchymal stem cells (MSCs) and dental pulp stem cells (DPSCs) from NK cell mediated cytotoxicity. PLoS One. 2010;5:e9874.CrossRef
30.
Rodas-Junco BA, Canul-Chan M, Rojas-Herrera RA, De-la-Pena C, Nic-Can GI. Stem cells from dental pulp: what epigenetics can do with your tooth. Front Physiol. 2017;8:999.CrossRef
31.
Sanen K, Martens W, Georgiou M, Ameloot M, Lambrichts I, et al. Engineered neural tissue with Schwann cell differentiated human dental pulp stem cells: potential for peripheral nerve repair? J Tissue Eng Regen Med. 2017;11:3362–72.CrossRef
32.
Soares DG, Rosseto HL, Scheffel DS, Basso FG, Huck C, et al. Odontogenic differentiation potential of human dental pulp cells cultured on a calcium-aluminate enriched chitosan-collagen scaffold. Clin Oral Investig. 2017;21:2827–39.CrossRef
33.
Song JS, Takimoto K, Jeon M, Vadakekalam J, Ruparel NB, et al. Decellularized human dental pulp as a scaffold for regenerative endodontics. J Dent Res. 2017;96:640–6.CrossRef
34.
Song M, Lee JH, Bae J, Bu Y, Kim EC. Human dental pulp stem cells are more effective than human bone marrow-derived mesenchymal stem cells in cerebral ischemic injury. Cell Transplant. 2017;26:1001–16.CrossRef
35.
Gordeuk VR. Osteoclast activation and sickle bone disease. Blood. 2015;126:2259–60.CrossRef
36.
Jiang H, Wang Y, Viniegra A, Sima C, McCulloch CA, et al. Adseverin plays a role in osteoclast differentiation and periodontal disease-mediated bone loss. FASEB J. 2015;29:2281–91.CrossRef
37.
Mucci JM, Suqueli Garcia F, de Francesco PN, Ceci R, Di Genaro S, et al. Uncoupling of osteoblast-osteoclast regulation in a chemical murine model of Gaucher disease. Gene. 2013;532:186–91.CrossRef
38.
Boyce BF, Rosenberg E, de Papp AE, Duong LT. The osteoclast, bone remodelling and treatment of metabolic bone disease. Eur J Clin Investig. 2012;42:1332–41.CrossRef
39.
Singer FR, Leach RJ. Bone: do all Paget disease risk genes incriminate the osteoclast? Nat Rev Rheumatol. 2010;6:502–3.CrossRef
40.
Iwami K, Moriyama T. Effects of short chain fatty acid, sodium butyrate, on osteoblastic cells and osteoclastic cells. Int J BioChemiPhysics. 1993;25:1631–5.CrossRef
41.
El-Serafi AT, Oreffo RO, Roach HI. Epigenetic modifiers influence lineage commitment of human bone marrow stromal cells: differential effects of 5-aza-deoxycytidine and trichostatin a. Differentiation. 2011;81:35–41.CrossRef
42.
Kim HN, Ha H, Lee JH, Jung K, Yang D, et al. Trichostatin a inhibits osteoclastogenesis and bone resorption by suppressing the induction of c-Fos by RANKL. Eur J Pharmacol. 2009;623:22–9.CrossRef
43.
Ali SA, Dobson JR, Lian JB, Stein JL, van Wijnen AJ, et al. A RUNX2-HDAC1 co-repressor complex regulates rRNA gene expression by modulating UBF acetylation. J Cell Sci. 2012;125:2732–9.CrossRef
44.
Schroeder TM, Kahler RA, Li X, Westendorf JJ. Histone deacetylase 3 interacts with runx2 to repress the osteocalcin promoter and regulate osteoblast differentiation. J Biol Chem. 2004;279:41998–2007.CrossRef
45.
Westendorf JJ, Zaidi SK, Cascino JE, Kahler R, van Wijnen AJ, et al. Runx2 (Cbfa1, AML-3) interacts with histone deacetylase 6 and represses the p21(CIP1/WAF1) promoter. Mol Cell Biol. 2002;22:7982–92.CrossRef
46.
Jensen ED, Schroeder TM, Bailey J, Gopalakrishnan R, Westendorf JJ. Histone deacetylase 7 associates with Runx2 and represses its activity during osteoblast maturation in a deacetylation-independent manner. J Bone Miner Res. 2008;23:361–72.CrossRef
47.
Pham L, Kaiser B, Romsa A, Schwarz T, Gopalakrishnan R, et al. HDAC3 and HDAC7 have opposite effects on osteoclast differentiation. J Biol Chem. 2011;286:12056–65.CrossRef
48.
Jin Z, Wei W, Dechow PC, Wan Y. HDAC7 inhibits osteoclastogenesis by reversing RANKL-triggered beta-catenin switch. Mol Endocrinol. 2013;27:325–35.CrossRef
49.
Zhang CL, McKinsey TA, Chang S, Antos CL, Hill JA, et al. Class II histone deacetylases act as signal-responsive repressors of cardiac hypertrophy. Cell. 2002;110:479–88.CrossRef
50.
Cohen-Kfir E, Artsi H, Levin A, Abramowitz E, Bajayo A, et al. Sirt1 is a regulator of bone mass and a repressor of Sost encoding for sclerostin, a bone formation inhibitor. Endocrinology. 2011;152:4514–24.CrossRef
51.
Luxton GW, Gundersen GG. HDAC6-pack: cortactin acetylation joins the brew. Dev Cell. 2007;13:161–2.CrossRef
52.
Zhang X, Yuan Z, Zhang Y, Yong S, Salas-Burgos A, et al. HDAC6 modulates cell motility by altering the acetylation level of cortactin. Mol Cell. 2007;27:197–213.CrossRef
53.
Rao R, Fiskus W, Yang Y, Lee P, Joshi R, et al. HDAC6 inhibition enhances 17-AAG--mediated abrogation of hsp90 chaperone function in human leukemia cells. Blood. 2008;112:1886–93.CrossRef
54.
Kovacs JJ, Murphy PJ, Gaillard S, Zhao X, Wu JT, et al. HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell. 2005;18:601–7.CrossRef
55.
Ota S, Zhou ZQ, Romero MP, Yang G, Hurlin PJ. HDAC6 deficiency or inhibition blocks FGFR3 accumulation and improves bone growth in a model of achondroplasia. Hum Mol Genet. 2017;26:3651.CrossRef
56.
Ota S, Zhou ZQ, Romero MP, Yang G, Hurlin PJ. HDAC6 deficiency or inhibition blocks FGFR3 accumulation and improves bone growth in a model of achondroplasia. Hum Mol Genet. 2016;25:4227–43.CrossRef
Metadata
Title
HDAC6 regulates dental mesenchymal stem cells and osteoclast differentiation
Authors
Yi Wang
Zhi Yun Shi
Jin Feng
Jun Kai Cao
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Oral Health / Issue 1/2018
Electronic ISSN: 1472-6831
DOI
https://doi.org/10.1186/s12903-018-0624-1

Other articles of this Issue 1/2018

BMC Oral Health 1/2018 Go to the issue

Research article

Novel caries loci in children and adults implicated by genome-wide analysis of families

Research article

Consequences of community water fluoridation cessation for Medicaid-eligible children and adolescents in Juneau, Alaska

Research article

Income and wealth as correlates of socioeconomic disparity in dentist visits among adults aged 20 years and over in the United States, 2011–2014

Research article

The effects of at-home whitening on patients’ oral health, psychology, and aesthetic perception

Research article

Validity assessment of quantitative light-induced fluorescence-digital (QLF-D) for the dental plaque scoring system: a cross-sectional study

Research article

Comparison of glide paths created with K-files, PathFiles, and the ProGlider file, and their effects on subsequent WaveOne preparation in curved canals