PP2A regulatory subunit B55γ is a gatekeeper of osteoblast maturation and lineage maintenance
Abstract
Bone marrow mesenchymal stem cells (BM-MSCs) mediate skeletal remodeling by differentiating into osteoblasts. However, this remodeling is impaired with aging as well as following long-term glucocorticoid treatment, resulting in osteoporosis. In this study, we report a novel factor of osteoblast differentiation-PP2A regulatory subunit B55γ. We show that B55γ is induced by glucocorticoid receptor (GR) in human primary BM-MSCs during differentiation to osteoblast, but not to adipocytes, and is required for osteoblast morphogenesis and mineralization. Moreover, B55γ knockdown under osteogenic conditions leads to the accumulation of lipid droplets in a subset of BM-MSCs. Treatment of BM-MSCs with only GR ligand dexamethasone induces B55γ transcript, but not protein, and causes widespread generation of lipid droplets. These data indicate that B55γ is an essential factor of osteoblast lineage, acting as a gatekeeper downstream of master regulators. This opens a new direction of research for understanding mechanisms of glucocorticoid-induced osteoporosis and bone marrow adiposity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Knockdown of B55γ in bone marrow mesenchymal stem cells reduces mineralization, calcium deposits and cuboidal morphology.
“Knockdown of B55γ in BM-MSCs reduced mineralization with insufficient calcium depoisits and a lack of the characteristic cuoidal cell morphology (Serguienko et al., 2017).”
From PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer (2019) · cites this paper as Serguienko et al., 2017
The PP2A-B55 phosphatase complex plays a pivotal role in cell cycle control, with the B55γ subunit emerging as a linchpin in developmental and oncogenic pathways.
“Notably, the PP2A-B55 phosphatase complex plays a pivotal role in cell cycle control, with the B55γ subunit (encoded by PPP2R2C ) emerging as a linchpin in developmental and oncogenic pathways.”
From Targeting PP2A in cancer: an underrated option (2025) · cites this paper as [264]
Cites
Serine/threonine phosphatases: mechanism through structure
Shi, Y. (2009) · Cell · doi:10.1016/j.cell.2009.10.006 · Cited by 1,488 · see citing works
Feng, X., & McDonald, J. M. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130203 · Cited by 1,272 · see citing works
Clinical Orthopaedics and Related Research
TL (1966) · The American Journal of the Medical Sciences · doi:10.1097/00000441-196607000-00044 · Cited by 895 · see citing works
Sontag, E., Nunbhakdi‐Craig, V., Lee, G. S., Bloom, G. S., & Mumby, M. C. (1996) · Neuron · doi:10.1016/s0896-6273(00)80250-0 · Cited by 391 · see citing works
Mechanism of glucocorticoid receptor down-regulation by glucocorticoids.
Rosewicz, S., McDonald, A. R., Maddux, B. A., Goldfine, I. D., Miesfeld, R. L., & Logsdon, C. D. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)69104-5 · Cited by 322 · see citing works
Glucocorticoid Receptor Phosphorylation Differentially Affects Target Gene Expression
Chen, W., Dang, T., Blind, R. D., Wang, Z., Cavasotto, C. N., Hittelman, A. B., Rogatsky, I., Logan, S. K., & Garabedian, M. J. (2008) · Molecular Endocrinology · doi:10.1210/me.2007-0219 · Cited by 280 · see citing works
Cellular and Molecular Biology of Bone
(1993) · Elsevier eBooks · doi:10.1016/c2009-0-02411-8 · Cited by 253 · see citing works
Itoh, M., Adachi, M., Yasui, H., Takekawa, M., Tanaka, H., & Imai, K. (2002) · Molecular Endocrinology · doi:10.1210/me.2002-0144 · Cited by 238 · see citing works
Strack, S., Zaucha, J. A., Ebner, F. F., Colbran, R. J., & Wadzinski, B. E. (1998) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19980323)392:4 · Cited by 181 · see citing works
Li, J., Zhang, N., Huang, X.-C., Xu, J.-K., Fernandes, J., Dai, K., & Zhang, X.-L. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.348 · Cited by 180 · see citing works
Silva, C. M., Powell-Oliver, F. E., Jewell, C. M., Sar, M., Allgood, V., & Cidlowski, J. A. (1994) · Steroids · doi:10.1016/0039-128x(94)90013-2 · Cited by 128 · see citing works
The Regulatory Landscape of Osteogenic Differentiation
Håkelien, A.-M., Bryne, J. C., Harstad, K. G., Lorenz, S., Paulsen, J., Sun, J., Mikkelsen, T. S., Myklebost, O., & Meza‐Zepeda, L. A. (2014) · Stem Cells · doi:10.1002/stem.1759 · Cited by 105 · see citing works
Self-citationDefects of Protein Phosphatase 2A Causes Corticosteroid Insensitivity in Severe Asthma
Kobayashi, Y., Mercado, N., Barnes, P. J., & Ito, K. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027627 · Cited by 96 · see citing works
Dagda, R. K., Zaucha, J. A., Wadzinski, B. E., & Strack, S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302832200 · Cited by 92 · see citing works
McNeill, R. B., & Colbran, R. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.17.10043 · Cited by 89 · see citing works
Protein Phosphatase 2A Holoenzyme Assembly
Strack, S., Ruediger, R., Walter, G., Dagda, R. K., Barwacz, C. A., & Cribbs, J. T. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202992200 · Cited by 83 · see citing works
Strack, S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203767200 · Cited by 81 · see citing works
Metabolic reprogramming of metastatic breast cancer and melanoma bylet-7amicroRNA
Serguienko, A., Grad, I., Wennerström, A. B., Meza‐Zepeda, L. A., Thiede, B., Stratford, E. W., Myklebost, O., & Munthe, E. (2014) · Oncotarget · doi:10.18632/oncotarget.3235 · Cited by 76 · see citing works
Self-citationMorimoto, Y., Ohba, T., Kobayashi, S., et al. (1997) · Experimental Cell Research · doi:10.1006/excr.1996.3404 · Cited by 76 · see citing works
Park, J. (2010) · Journal of Surgical Research · doi:10.1016/j.jss.2010.09.010 · Cited by 72 · see citing works
Patel, J. J., Butters, O., & Arnett, T. R. (2014) · Cell Biochemistry and Function · doi:10.1002/cbf.3025 · Cited by 63 · see citing works
Generation and Characterization of an Immortalized Human Mesenchymal Stromal Cell Line
Skårn, M., Noordhuis, P., Wang, M.-Y., Veuger, M. J. T., Kresse, S. H., Egeland, E. V., Micci, F., Namløs, H. M., Håkelien, A.-M., Olafsrud, S. M., et al. (2014) · Stem Cells and Development · doi:10.1089/scd.2013.0599 · Cited by 52 · see citing works
Self-citationMechanism of De Novo Mineral Formation by Matrix Vesicles
Wuthier, R. E. (1989) · Connective Tissue Research · doi:10.3109/03008208909114117 · Cited by 50 · see citing works
MiR-572 prompted cell proliferation of human ovarian cancer cells by suppressing PPP2R2C expression
Wu, A., Huang, Y., Zhang, L., Tian, G., Liao, Q.-Z., & Chen, S. (2015) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2015.12.005 · Cited by 44 · see citing works
miR-1301 promotes prostate cancer proliferation through directly targeting PPP2R2C
Bi, D., Ning, H., Liu, S., Que, X., & Ding, K. (2016) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2016.03.043 · Cited by 40 · see citing works
Catechin stimulates osteogenesis by enhancing PP2A activity in human mesenchymal stem cells
Wei, Y., Tsai, K., Lin, L.-C., et al. (2010) · Osteoporosis International · doi:10.1007/s00198-010-1352-9 · Cited by 39 · see citing works
Berkovitz, G. D., Carter, K. M., Migeon, C. J., et al. (1988) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-66-5-1029 · Cited by 31 · see citing works
Bruedigam, C., Koedam, M., Chiba, H., et al. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.04.012 · Cited by 31 · see citing works
Role of Protein Phosphatase 2A in Osteoblast Differentiation and Function
Okamura, H., Yoshida, K., Morimoto, H., Teramachi, J., Ochiai, K., Haneji, T., & Yamamoto, A. (2017) · Journal of Clinical Medicine · doi:10.3390/jcm6030023 · Cited by 28 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer
(2019) · Advances in Cancer Research · doi:10.1016/bs.acr.2019.03.009 · Cited by 93 · see citing works
Targeting PP2A in cancer: an underrated option
Sarais, F., Krempien, F., Koehn, C., Brewing, L., Classen, C. F., Walter, M., & Shokraie, O. (2025) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-025-03560-y · Cited by 8 · see citing works
- Authors
- Serguienko, A., Hanes, R., Grad, I., Wang, M. Y., Myklebost, O., & Munthe, E.
- Affiliations
- Oslo University Hospital (NO)
- Corresponding author
- Serguienko, Anastassia
- Munthe, Else
- Venue
- Stem Cells and Development
- Publisher
- SAGE Publications
- Published
- 2017-10
- Volume
- 26
- Issue
- 19
- Pages
- 1375-1383
- ISSN
- 1525-8165 (ISSN-L)
- 1547-3287
- 1557-8534
- OpenAlex
- W2745069629
- Cited by
- 9
- References
- 29
- Citations by year
- 2025: 3 · 2020: 2 · 2019: 2 · 2018: 2
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Stem Cells and Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Rochester
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- osteogenic differentiation, bone marrow mesenchymal stem cells, glucocorticoid receptor, glucocorticoid-induced osteoporosis, bone marrow adiposity, lipid droplets, mineralization, dexamethasone, aging
- MeSH terms
- Cell Differentiation, Cells, Cultured, Female, Humans, Male, Osteoblasts, Receptors, Glucocorticoid, Cell Lineage, Protein Subunits, Protein Phosphatase 2, Mesenchymal Stem Cells, Lipid Droplets
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
