Extracellular PPM1A Promotes Mineralization of Osteoblasts Differentiation in Ankylosing Spondylitis Via the FOXO1A-RUNX2 Pathway

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2023 Feb 9

PMID 36756789

Authors

Subin Weon

Sungsin Jo

Bora Nam

Sung Hoon Choi

Ye-Soo Park

Yong-Gil Kim

Tae-Hwan Kim

Affiliations

Soon will be listed here.

Abstract

Protein phosphatase magnesium-dependent 1A (PPM1A), serine/threonine protein phosphatase, in sera level was increased in patients with ankylosing spondylitis (AS). Preosteoblasts were differentiated actively to matured osteoblasts by intracellular PPM1A overexpression. However, it was unclear whether extracellular PPM1A contributes to the excessive bone-forming activity in AS. Here, we confirmed that PPM1A and runt-related transcription factor 2 (RUNX2) were increased in facet joints of AS. During osteoblasts differentiation, exogenous PPM1A treatment showed increased matrix mineralization in AS-osteoprogenitor cells accompanied by induction of RUNX2 and factor forkhead box O1A (FOXO1A) protein expressions. Moreover, upon growth condition, exogenous PPM1A treatment showed an increase in RUNX2 and FOXO1A protein expression and a decrease in phosphorylation at ser256 of FOXO1A protein in AS-osteoprogenitor cells, and positively regulated promoter activity of RUNX2 protein-binding motif. Mechanically, exogenous PPM1A treatment induced the dephosphorylation of transcription factor FOXO1A protein and translocation of FOXO1A protein into the nucleus for RUNX2 upregulation. Taken together, our results suggest that high PPM1A concentration promotes matrix mineralization in AS via the FOXO1A-RUNX2 pathway.

Citing Articles

Knockdown of SIGLEC1 inhibits osteogenic differentiation to alleviate ankylosing spondylitis progression by suppressing the TGF-β1/SMAD signaling pathway.

Chen J, Yang X, Huang Y, Cao X, Wu Z, Feng Y Naunyn Schmiedebergs Arch Pharmacol. 2024; .

PMID: 39305328 DOI: 10.1007/s00210-024-03456-2.

Extracellular PPM1A promotes mineralization of osteoblasts differentiation in ankylosing spondylitis via the FOXO1A-RUNX2 pathway.

Weon S, Jo S, Nam B, Choi S, Park Y, Kim Y J Cell Mol Med. 2023; 27(5):650-658.

PMID: 36756789 PMC: 9983316. DOI: 10.1111/jcmm.17685.

References

Jo S, Nam B, Lee Y, Park H, Weon S, Choi S . The TNF-NF-kB-DKK1 Axis Promoted Bone Formation in the Enthesis of Ankylosing Spondylitis. J Rheum Dis. 2023; 28(4):216-224. PMC: 10324906. DOI: 10.4078/jrd.2021.28.4.216. View

Kim Y, Sohn D, Zhao X, Sokolove J, Lindstrom T, Yoo B . Role of protein phosphatase magnesium-dependent 1A and anti-protein phosphatase magnesium-dependent 1A autoantibodies in ankylosing spondylitis. Arthritis Rheumatol. 2014; 66(10):2793-2803. PMC: 4198528. DOI: 10.1002/art.38763. View

Tam L, Gu J, Yu D . Pathogenesis of ankylosing spondylitis. Nat Rev Rheumatol. 2010; 6(7):399-405. DOI: 10.1038/nrrheum.2010.79. View

Atas Y, Zhang J, Lewis R, Jahanpour A, Haase J, Muschik C . SU(2) hadrons on a quantum computer via a variational approach. Nat Commun. 2021; 12(1):6499. PMC: 8586147. DOI: 10.1038/s41467-021-26825-4. View

Lee J, Lee E, Lee J, Hong S, Lee C, Yoo B . Autoantibodies against Protein Phosphatase Magnesium-Dependent 1A as a Biomarker for Predicting Radiographic Progression in Ankylosing Spondylitis Treated with Anti-Tumor Necrosis Factor Agents. J Clin Med. 2020; 9(12). PMC: 7762424. DOI: 10.3390/jcm9123968. View

Teixeira C, Liu Y, Thant L, Pang J, Palmer G, Alikhani M . Foxo1, a novel regulator of osteoblast differentiation and skeletogenesis. J Biol Chem. 2010; 285(40):31055-65. PMC: 2945596. DOI: 10.1074/jbc.M109.079962. View

Kwon S . The Long, Dynamic Journey to the Elucidation of the Links Between Inflammation, Ectopic Bone Formation, and Wnt Signaling in Ankylosing Spondylitis. J Rheum Dis. 2023; 29(1):1-3. PMC: 10324921. DOI: 10.4078/jrd.2022.29.1.1. View

Sergi C, Shen F, Liu S . Insulin/IGF-1R, SIRT1, and FOXOs Pathways-An Intriguing Interaction Platform for Bone and Osteosarcoma. Front Endocrinol (Lausanne). 2019; 10:93. PMC: 6405434. DOI: 10.3389/fendo.2019.00093. View

Jo S, Wang S, Lee Y, Kang S, Lee B, Han J . IL-17A induces osteoblast differentiation by activating JAK2/STAT3 in ankylosing spondylitis. Arthritis Res Ther. 2018; 20(1):115. PMC: 5992730. DOI: 10.1186/s13075-018-1582-3. View

10.

Tsai W, Bhattacharyya N, Han L, Hanover J, Rechler M . Insulin inhibition of transcription stimulated by the forkhead protein Foxo1 is not solely due to nuclear exclusion. Endocrinology. 2003; 144(12):5615-22. DOI: 10.1210/en.2003-0481. View

11.

Inman R . Axial Spondyloarthritis: Current Advances, Future Challenges. J Rheum Dis. 2023; 28(2):55-59. PMC: 10324891. DOI: 10.4078/jrd.2021.28.2.55. View

12.

Grandon B, Rincheval-Arnold A, Jah N, Corsi J, Araujo L, Glatigny S . HLA-B27 alters BMP/TGFβ signalling in , revealing putative pathogenic mechanism for spondyloarthritis. Ann Rheum Dis. 2019; 78(12):1653-1662. DOI: 10.1136/annrheumdis-2019-215832. View

13.

Accili D, Arden K . FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell. 2004; 117(4):421-6. DOI: 10.1016/s0092-8674(04)00452-0. View

14.

Lories R, Luyten F . Bone morphogenetic protein signaling in joint homeostasis and disease. Cytokine Growth Factor Rev. 2005; 16(3):287-98. DOI: 10.1016/j.cytogfr.2005.02.009. View

15.

Bleil J, Sieper J, Maier R, Schlichting U, Hempfing A, Syrbe U . Cartilage in facet joints of patients with ankylosing spondylitis (AS) shows signs of cartilage degeneration rather than chondrocyte hypertrophy: implications for joint remodeling in AS. Arthritis Res Ther. 2015; 17:170. PMC: 4506408. DOI: 10.1186/s13075-015-0675-5. View

16.

Lories R, Derese I, Luyten F . Modulation of bone morphogenetic protein signaling inhibits the onset and progression of ankylosing enthesitis. J Clin Invest. 2005; 115(6):1571-9. PMC: 1090472. DOI: 10.1172/JCI23738. View

17.

Brunet A, Bonni A, Zigmond M, Lin M, Juo P, Hu L . Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999; 96(6):857-68. DOI: 10.1016/s0092-8674(00)80595-4. View

18.

Braun J, Sieper J . Ankylosing spondylitis. Lancet. 2007; 369(9570):1379-1390. DOI: 10.1016/S0140-6736(07)60635-7. View

19.

Mummidi S, Das N, Carpenter A, Kandikattu H, Krenz M, Siebenlist U . Metformin inhibits aldosterone-induced cardiac fibroblast activation, migration and proliferation in vitro, and reverses aldosterone+salt-induced cardiac fibrosis in vivo. J Mol Cell Cardiol. 2016; 98:95-102. DOI: 10.1016/j.yjmcc.2016.07.006. View

20.

Weon S, Jo S, Nam B, Choi S, Park Y, Kim Y . Extracellular PPM1A promotes mineralization of osteoblasts differentiation in ankylosing spondylitis via the FOXO1A-RUNX2 pathway. J Cell Mol Med. 2023; 27(5):650-658. PMC: 9983316. DOI: 10.1111/jcmm.17685. View