Skip to main content

Advertisement

SpringerLink
Log in

Sirtuin 6 ameliorates arthritis through modulating cyclic AMP-responsive element binding protein/CCN1/cyclooxygenase 2 pathway in osteoblasts

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Introduction

CCN1 is an immediate-early gene product pivotal for arthritis progression. We have previously shown that sirtuin 6 (SIRT6) inhibited hypoxia-induced CCN1 expression in osteoblasts. Herein we examined the contribution of cyclic AMP-responsive element binding protein (CREB)/CRE to this suppressive action and the influence of CCN1 on cyclooxygenase (COX) 2 synthesis.

Materials and methods

MC3T3-E1 murine osteoblasts were cultured under normoxia (21% oxygen) or hypoxia (2% oxygen). Expressions of CCN1, phospho-CREB (Ser133), COX2 and relevant kinases were assessed by Western blot. SIRT6 was overexpressed in cultured osteoblasts and arthritic joints by a lentiviral-based technique. Activities of CCN1 gene promoter constructs were examined by luciferase reporter assay. Interaction between CREB and CCN1 promoter was assessed by chromatin immunoprecipitation (ChIP). Collagen-induced arthritis (CIA) was established in 20 rats to evaluate the effects of SIRT6 therapy on osteoblastic expressions of phospho-CREB, CCN1 and COX2.

Results

SIRT6 suppressed hypoxia-enhanced CCN1 expression and CREB phosphorylation. Attenuation of calcium/calmodulin-dependent protein kinase II (CaMKII) may be responsible for SIRT6-induced CREB inhibition. CRE at − 286 bp upstream of the ATG start codon was essential for CCN1 expression under hypoxia and SIRT6 reduced hypoxia-stimulated CREB/CRE interaction. Forced expression of CREB rescued SIRT6-suppressed CCN1 synthesis. CCN1 induced COX2 expression in osteoblasts. In rat CIA, the therapeutic effect of SIRT6 was accompanied by decreases in osteoblastic expressions of phospho-CREB, CCN1 and COX2.

Conclusion

Our study indicated that the benefits of SIRT6 to inflammatory arthritis and bone resorption are at least partially derived from its modulation of CREB/CCN1/COX2 pathway in osteoblasts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Emre Y, Imhof BA (2014) Matricellular protein CCN1/CYR61: a new player in inflammation and leukocyte trafficking. Semin Immunopathol 36:253–259

    Article  CAS  PubMed  Google Scholar 

  2. Xu T, He YH, Wang MQ, Yao HW, Ni MM, Zhang L, Meng XM, Huang C, Ge YX, Li J (2016) Therapeutic potential of cysteine-rich protein 61 in rheumatoid arthritis. Gene 592:179–185

    Article  CAS  PubMed  Google Scholar 

  3. Kok SH, Hou KL, Hong CY, Wang JS, Liang PC, Chang CC, Hsiao M, Yang H, Lai EH, Lin SK (2011) Simvastatin inhibits cytokine-stimulated Cyr61 expression in osteoblastic cells: a therapeutic benefit for arthritis. Arthritis Rheum 63:1010–1020

    Article  CAS  PubMed  Google Scholar 

  4. Kok SH, Lin LD, Hou KL, Hong CY, Chang CC, Hsiao M, Wang JH, Lai EH, Lin SK (2013) Simvastatin inhibits cysteine-rich protein 61 expression in rheumatoid arthritis synovial fibroblasts through the regulation of sirtuin-1/FoxO3a signaling. Arthritis Rheum 65:639–649

    Article  CAS  PubMed  Google Scholar 

  5. Yang Y, Zhu M, Liang J, Wang H, Sun D, Li H, Chen L (2022) SIRT6 mediates multidimensional modulation to maintain organism homeostasis. J Cell Physiol 237:3205–3221

    Article  CAS  PubMed  Google Scholar 

  6. Liu G, Chen H, Liu H, Zhang W, Zhou J (2021) Emerging roles of SIRT6 in human diseases and its modulators. Med Res Rev 41:1089–1137

    Article  PubMed  Google Scholar 

  7. Lee HS, Ka SO, Lee SM, Lee SI, Park JW, Park BH (2013) Overexpression of sirtuin 6 suppresses inflammatory responses and bone destruction in mice with collagen-induced arthritis. Arthritis Rheum 65:1776–1785

    Article  CAS  PubMed  Google Scholar 

  8. Hou KL, Lin SK, Chao LH, Lai EH, Chang CC, Shun CT, Lu WY, Wang JH, Hsiao M, Hong CY, Kok SH (2017) Sirtuin 6 suppresses hypoxia-induced inflammatory response in human osteoblasts via inhibition of reactive oxygen species production and glycolysis-A therapeutic implication in inflammatory bone resorption. BioFactors 43:170–180

    Article  CAS  PubMed  Google Scholar 

  9. Eltzschig HK, Carmeliet P (2011) Hypoxia and inflammation. N Engl J Med 364:656–665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Falchuk KH, Goetzl EJ, Kulka JP (1970) Respiratory gases of synovial fluids. An approach to synovial tissue circulatory-metabolic imbalance in rheumatoid arthritis. Am J Med 49:223–231

    Article  CAS  PubMed  Google Scholar 

  11. Lund-Olesen K (1970) Oxygen tension in synovial fluids. Arthritis Rheum 13:769–776

    Article  CAS  PubMed  Google Scholar 

  12. Meyuhas R, Pikarsky E, Tavor E, Klar A, Abramovitch R, Hochman J, Lago TG, Honigman A (2008) A key role for cyclic AMP-responsive element binding protein in hypoxia-mediated activation of the angiogenesis factor CCN1 (CYR61) in tumor cells. Mol Cancer Res 6:1397–1409

    Article  CAS  PubMed  Google Scholar 

  13. Schütze N, Rucker N, Muller J, Adamski J, Jakob F (2001) 5’ flanking sequence of the human immediate early responsive gene ccn1 (cyr61) and mapping of polymorphic CA repeat sequence motifs in the human ccn1 (cyr61) locus. Mol Pathol 54:170–175

    Article  PubMed  PubMed Central  Google Scholar 

  14. Mendes KL, Lelis DF, Santos SHS (2017) Nuclear sirtuins and inflammatory signaling pathways. Cytokine Growth Factor Rev 38:98–105

    Article  CAS  PubMed  Google Scholar 

  15. Li Y, Jin J, Wang Y (2022) SIRT6 widely regulates aging, immunity, and cancer. Front Oncol 12:861334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Nishikawa K, Seno S, Yoshihara T, Narazaki A, Sugiura Y et al (2021) Osteoclasts adapt to physioxia perturbation through DNA demethylation. EMBO Rep 22:e53035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Narazaki A, Shimizu R, Yoshihara T, Kikuta J, Sakaguchi R, Tobita S, Mori Y, Ishii M, Nishikawa K (2022) Determination of the physiological range of oxygen tension in bone marrow monocytes using two-photon phosphorescence lifetime imaging microscopy. Sci Rep 12:3497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chen CY, Fuh LJ, Huang CC, Hsu CJ, Su CM, Liu SC, Lin YM, Tang CH (2017) Enhancement of CCL2 expression and monocyte migration by CCN1 in osteoblasts through inhibiting miR-518a-5p: implication of rheumatoid arthritis therapy. Sci Rep 7:421

    Article  PubMed  PubMed Central  Google Scholar 

  19. He X, Liu J, Liang C, Badshah SA, Zheng K, Dang L, Guo B, Li D, Lu C, Guo Q, Fan D, Bian Y, Feng H, Xiao L, Pan X, Xiao C, Zhang B, Zhang G, Lu A (2019) Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritis. EBioMedicine 41:538–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Xiao J, Qin S, Li W, Yao L, Huang P, Liao J, Liu J, Li S (2020) Osteogenic differentiation of rat bone mesenchymal stem cells modulated by MiR-186 via SIRT6. Life Sci 253:117660

    Article  CAS  PubMed  Google Scholar 

  21. Kim SJ, Piao Y, Lee MG, Han AR, Kim K, Hwang CJ, Seo JT, Moon SJ (2020) Loss of Sirtuin 6 in osteoblast lineage cells activates osteoclasts, resulting in osteopenia. Bone 138:115497

    Article  CAS  PubMed  Google Scholar 

  22. Zhang Z, Song Y, Wang SI, Ha SH, Jang KY, Park BH, Moon YJ, Kim JR (2021) Osteoblasts/osteocytes sirtuin 6 is vital to preventing ischemic osteonecrosis through targeting VDR-RANKL signaling. J Bone Miner Res 36:579–590

    Article  CAS  PubMed  Google Scholar 

  23. Kok SH, Hou KL, Hong CY, Chao LH, Hsiang-Hua Lai E, Wang HW, Yang H, Shun CT, Wang JS, Lin SK (2015) Sirtuin 6 modulates hypoxia-induced apoptosis in osteoblasts via inhibition of glycolysis: implication for pathogenesis of periapical lesions. J Endod 41:1631–1637

    Article  PubMed  Google Scholar 

  24. Lee YL, Lin SK, Hou KL, Kok SH, Lai EH, Wang HW, Chang JZ, Yang H, Hong CY (2018) Sirtuin 6 attenuates periapical lesion propagation by modulating hypoxia-induced chemokine (C–C motif) ligand 2 production in osteoblasts. Int Endod J 51:e74–e86

    Article  PubMed  Google Scholar 

  25. Kawahara TL, Michishita E, Adler AS, Damian M, Berber E, Lin M, McCord RA, Ongaigui KC, Boxer LD, Chang HY, Chua KF (2009) SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span. Cell 136:62–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Xiao C, Wang RH, Lahusen TJ, Park O, Bertola A, Maruyama T, Reynolds D, Chen Q, Xu X, Young HA, Chen WJ, Gao B, Deng CX (2012) Progression of chronic liver inflammation and fibrosis driven by activation of c-JUN signaling in Sirt6 mutant mice. J Biol Chem 287:41903–41913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Grimley R, Polyakova O, Vamathevan J, McKenary J, Hayes B, Patel C, Smith J, Bridges A, Fosberry A, Bhardwaja A, Mouzon B, Chung CW, Barrett N, Richmond N, Modha S, Solari R (2012) Over expression of wild type or a catalytically dead mutant of sirtuin 6 does not influence NFκB responses. PLoS ONE 7:e39847

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wakisaka S, Suzuki N, Takeno M, Takeba Y, Nagafuchi H, Saito N, Hashimoto H, Tomita T, Ochi T, Sakane T (1998) Involvement of simultaneous multiple transcription factor expression, including cAMP responsive element binding protein and OCT-1, for synovial cell outgrowth in patients with rheumatoid arthritis. Ann Rheum Dis 57:487–494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. McEvoy AN, Bresnihan B, FitzGerald O, Murphy EP (2004) Cyclooxygenase 2-derived prostaglandin E2 production by corticotropin-releasing hormone contributes to the activated cAMP response element binding protein content in rheumatoid arthritis synovial tissue. Arthritis Rheum 50:1132–1145

    Article  CAS  PubMed  Google Scholar 

  30. Song MY, Han CY, Moon YJ, Lee JH, Bae EJ, Park BH (2022) Sirt6 reprograms myofibers to oxidative type through CREB-dependent Sox6 suppression. Nat Commun 13:1808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zhang R, Li H, Guo Q, Zhang L, Zhu J, Ji J (2018) Sirtuin6 inhibits c-triggered inflammation through TLR4 abrogation regulated by ROS and TRPV1/CGRP. J Cell Biochem 119:9141–9153

    Article  CAS  PubMed  Google Scholar 

  32. Pan Z, Wu X, Zhang X, Hu K (2023) Phosphodiesterase 4B activation exacerbates pulmonary hypertension induced by intermittent hypoxia by regulating mitochondrial injury and cAMP/PKA/p-CREB/PGC-1α signaling. Biomed Pharmacother 158:114095

    Article  CAS  PubMed  Google Scholar 

  33. Li C, Tian J, Li G, Jiang W, Xing Y, Hou J, Zhu H, Xu H, Zhang G, Liu Z, Ye Z (2010) Asperosaponin VI protects cardiac myocytes from hypoxia-induced apoptosis via activation of the PI3K/Akt and CREB pathways. Eur J Pharmacol 649:100–107

    Article  CAS  PubMed  Google Scholar 

  34. Kushwah N, Jain V, Kadam M, Kumar R, Dheer A, Prasad D, Kumar B, Khan N (2021) Ginkgo biloba L. prevents hypobaric hypoxia-induced spatial memory deficit through small conductance calcium-activated potassium channel inhibition: the role of ERK/CaMKII/CREB signaling. Front Pharmacol 12:669701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Erickson JR, Joiner ML, Guan X, Kutschke W, Yang J, Oddis CV, Bartlett RK, Lowe JS, O’Donnell SE, Aykin-Burns N, Zimmerman MC, Zimmerman K, Ham AJ, Weiss RM, Spitz DR, Shea MA, Colbran RJ, Mohler PJ, Anderson ME (2008) A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell 133:462–474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Erickson JR, Pereira L, Wang L, Han G, Ferguson A, Dao K, Copeland RJ, Despa F, Hart GW, Ripplinger CM, Bers DM (2013) Diabetic hyperglycaemia activates CaMKII and arrhythmias by O-linked glycosylation. Nature 502:372–376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kishimoto K, Terabe K, Takahashi N, Yokota Y, Ohashi Y, Hattori K, Kihira D, Maeda M, Kojima T, Imagama S (2021) Metabolic changes in synovial cells in early inflammation: Involvement of CREB phosphorylation in the anti-inflammatory effect of 2-deoxyglucose. Arch Biochem Biophys 708:108962

    Article  CAS  PubMed  Google Scholar 

  38. Jiang H, Wei H, Wang H, Wang Z, Li J, Ou Y, Xiao X, Wang W, Chang A, Sun W, Zhao L, Yang S (2022) Zeb1-induced metabolic reprogramming of glycolysis is essential for macrophage polarization in breast cancer. Cell Death Dis 13:206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. La Spina M, Azzolini M, Salmaso A, Parrasia S, Galletta E, Schiavone M, Chrisam M, Mattarei A, Di Benedetto G, Ballabio A, Tiso N, Zoratti M, Biasutto L (2021) Multiple mechanisms converging on transcription factor EB activation by the natural phenol pterostilbene. Oxid Med Cell Longev 2021:7658501

    Article  PubMed  PubMed Central  Google Scholar 

  40. Seo E, Nam H, Jun HS (2022) Reactive oxygen species induce HNF-4α expression via the ASK1-CREB pathway, promoting ChREBP expression and lipogenesis in hepatocytes. Life Sci 310:121042

    Article  CAS  PubMed  Google Scholar 

  41. Song KS, Lee WJ, Chung KC, Koo JS, Yang EJ, Choi JY, Yoon JH (2003) Interleukin-1 beta and tumor necrosis factor-alpha induce MUC5AC overexpression through a mechanism involving ERK/p38 mitogen-activated protein kinases-MSK1-CREB activation in human airway epithelial cells. J Biol Chem 278:23243–23250

    Article  CAS  PubMed  Google Scholar 

  42. Hong OY, Jang HY, Lee YR, Jung SH, Youn HJ, Kim JS (2022) Inhibition of cell invasion and migration by targeting matrix metalloproteinase-9 expression via sirtuin 6 silencing in human breast cancer cells. Sci Rep 12:12125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Zhang S, Jiang S, Wang H, Di W, Deng C, Jin Z, Yi W, Xiao X, Nie Y, Yang Y (2018) SIRT6 protects against hepatic ischemia/reperfusion injury by inhibiting apoptosis and autophagy related cell death. Free Radic Biol Med 115:18–30

    Article  CAS  PubMed  Google Scholar 

  44. Shahgaldi S, Kahmini FR (2021) A comprehensive review of sirtuins: with a major focus on redox homeostasis and metabolism. Life Sci 282:119803

    Article  CAS  PubMed  Google Scholar 

  45. Kwon EJ, Park EJ, Yu H, Huh JS, Kim J, Cho M (2018) SIRT-1 regulates TGF-β-induced dermal fibroblast migration via modulation of Cyr61 expression. Connect Tissue Res 59:245–254

    CAS  PubMed  Google Scholar 

  46. Wei YJ, Wang JF, Cheng F, Xu HJ, Chen JJ, Xiong J, Wang J (2021) miR-124-3p targeted SIRT1 to regulate cell apoptosis, inflammatory response, and oxidative stress in acute myocardial infarction in rats via modulation of the FGF21/CREB/PGC1α pathway. J Physiol Biochem 77:577–587

    Article  CAS  PubMed  Google Scholar 

  47. Lu S, Yin X, Wang J, Gu Q, Huang Q, Jin N, Chu D, Xu Z, Liu F, Qian W (2020) SIRT1 regulates O-GlcNAcylation of tau through OGT. Aging (Albany NY) 12:7042–7055

    Article  CAS  PubMed  Google Scholar 

  48. Guclu E, Inan SY, Vural HC (2022) The sirtuin 2 inhibitor AK-7 leads to an antidepressant-like effect in mice via upregulation of CREB1, BDNF, and NTRK2 pathways. Mol Neurobiol 59:7036–7044

    Article  CAS  PubMed  Google Scholar 

  49. Shi T, Wang F, Stieren E, Tong Q (2005) SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes. J Biol Chem 280:13560–13567

    Article  CAS  PubMed  Google Scholar 

  50. O’Banion MK, Winn VD, Young DA (1992) cDNA cloning and functional activity of a glucocorticoid-regulated inflammatory cyclooxygenase. Proc Natl Acad Sci USA 89:4888–4892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kang RY, Freire-Moar J, Sigal E, Chu CQ (1996) Expression of cyclooxygenase-2 in human and an animal model of rheumatoid arthritis. Br J Rheumatol 35:711–718

    Article  CAS  PubMed  Google Scholar 

  52. Siegle I, Klein T, Backman JT, Saal JG, Nüsing RM, Fritz P (1998) Expression of cyclooxygenase 1 and cyclooxygenase 2 in human synovial tissue: differential elevation of cyclooxygenase 2 in inflammatory joint diseases. Arthritis Rheum 41:122–129

    Article  CAS  PubMed  Google Scholar 

  53. Anderson GD, Hauser SD, McGarity KL, Bremer ME, Isakson PC, Gregory SA (1996) Selective inhibition of cyclooxygenase (COX)-2 reverses inflammation and expression of COX-2 and interleukin 6 in rat adjuvant arthritis. J Clin Invest 97:2672–2679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Noguchi M, Kimoto A, Kobayashi S, Yoshino T, Miyata K, Sasamata M (2005) Effect of celecoxib, a cyclooxygenase-2 inhibitor, on the pathophysiology of adjuvant arthritis in rat. Eur J Pharmacol 513:229–235

    Article  CAS  PubMed  Google Scholar 

  55. Simon LS, Weaver AL, Graham DY, Kivitz AJ, Lipsky PE, Hubbard RC, Isakson PC, Verburg KM, Yu SS, Zhao WW, Geis GS (1999) Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized controlled trial. J Am Med Assoc 282:1921–1928

    Article  CAS  Google Scholar 

  56. Emery P, Zeidler H, Kvien TK, Guslandi M, Naudin R, Stead H, Verburg KM, Isakson PC, Hubbard RC, Geis GS (1999) Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison. Lancet 354:2106–2111

    Article  CAS  PubMed  Google Scholar 

  57. Lin MT, Zuon CY, Chang CC, Chen ST, Chen CP, Lin BR, Wang MY, Jeng YM, Chang KJ, Lee PH, Chen WJ, Kuo ML (2005) Cyr61 induces gastric cancer cell motility/invasion via activation of the integrin/nuclear factor-kappaB/cyclooxygenase-2 signaling pathway. Clin Cancer Res 11:5809–5820

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The work was supported by Grants from National Science and Technology Council, Taiwan (MOST 109-2314-B-002-034-MY3 to SHK and MOST 111-2314-B-002-113 to SKL) and National Taiwan University Hospital, Taipei, Taiwan (NTUH 109-S4494 and NTUH 110-S4841 to SHK and NTUH 109-S4746 and NTUH 111-S0140 to SKL).

Author information

Authors and Affiliations

  1. Department of Dentistry, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei, Taiwan

    Sze-Kwan Lin, Han-Wei Wang, Chi-Yuan Hong, Eddie Hsiang-Hua Lai, Shih-Jung Cheng, Mu-Hsiung Chen, Hsiang Yang, Hung-Ying Lin, Fang-Yu Wu & Sang-Heng Kok

  2. Department of Dentistry, School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan

    Sze-Kwan Lin, Cheng-Ning Yang, Chi-Yuan Hong, Eddie Hsiang-Hua Lai, Shih-Jung Cheng & Sang-Heng Kok

  3. Graduate Institute of Clinical Dentistry, School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan

    Han-Wei Wang

  4. Department of Forensic Medicine and Pathology, National Taiwan University Hospital, Taipei, Taiwan

    Chia-Tung Shun

  5. College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan

    Chi-Yuan Hong

Authors
  1. Sze-Kwan Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Han-Wei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chia-Tung Shun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cheng-Ning Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chi-Yuan Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eddie Hsiang-Hua Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shih-Jung Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mu-Hsiung Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hsiang Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hung-Ying Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Fang-Yu Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sang-Heng Kok
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SKL and SHK involved in study conception and design. HWW, CTS, CNY, CYH, EHHL, SJC, MHC, HY, HYL and FYW involved in data collection. SKL, HWW and SHK involved in the analysis and interpretation of data. SKL and SHK involved in manuscript preparation. All authors reviewed the results and approved the final version of the manuscript.

Corresponding author

Correspondence to Sang-Heng Kok.

Ethics declarations

Conflict of interest

The authors declare that there are no conflict of interest.

Ethical approval

The protocol of animal experiment was approved by the Laboratory Animal Center, College of Medicine, National Taiwan University.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

774_2023_1468_MOESM1_ESM.jpg

Supplementary file 1: Fig. 1. Overexpression of SIRT6 in murine osteoblasts. Cells were transduced with empty vector (pLVX) or pLVX-SIRT6 and stably transduced cells were selected by puromycin. SIRT6 expression was assessed by Western blot.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lin, SK., Wang, HW., Shun, CT. et al. Sirtuin 6 ameliorates arthritis through modulating cyclic AMP-responsive element binding protein/CCN1/cyclooxygenase 2 pathway in osteoblasts. J Bone Miner Metab 41, 772–784 (2023). https://doi.org/10.1007/s00774-023-01468-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-023-01468-1

Keywords

Search

Navigation