Reduction of protein phosphatase 2A Cα promotes in vivo bone formation and adipocyte differentiation

Kaya Yoshida, Jumpei Teramachi, Kenta Uchibe, Mika Ikegame, Lihong Qiu, Di Yang, Hirohiko Okamura

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Serine/threonine protein phosphatase 2A (PP2A) regulates diverse physiological processes such as cell cycle, growth, apoptosis, and signal transduction. Previously, we demonstrated that silencing of the α-isoform of PP2A catalytic subunit (PP2A Cα) in osteoblasts accelerated osteoblast differentiation, whereas its overexpression suppressed differentiation. In this study, we examined the role of PP2A Cα in in vivo bone formation by generating transgenic mice (PP2A-Tg), in which the dominant negative form of PP2A Cα was specifically expressed in osteoblasts. PP2A-Tg mice exhibited an increase in body weight, cortical bone mineral density, and cortical bone thickness. Interestingly, they also displayed higher amounts of adipose tissue in the bone marrow of tibiae. The co-culture study showed that PP2A Cα-knockdown osteoblasts stimulated adipocyte differentiation from undifferentiated mesenchymal cells via upregulation of the adipocyte marker genes, such as peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα). These results indicated that the reduction of PP2A Cα levels in osteoblasts promoted bone formation in vivo. Additionally, PP2A Cα in osteoblasts was also potentially involved in controlling adipocyte differentiation through a paracrine mechanism.

Original languageEnglish
JournalMolecular and Cellular Endocrinology
DOIs
Publication statusAccepted/In press - Jan 1 2017

Fingerprint

Protein Phosphatase 2
Phosphoprotein Phosphatases
Adipocytes
Osteogenesis
Bone
Osteoblasts
CCAAT-Enhancer-Binding Proteins
Physiological Phenomena
Signal transduction
Peroxisome Proliferator-Activated Receptors
Threonine
Coculture Techniques
Tibia
Cell culture
Bone Density
Serine
Transgenic Mice
Minerals
Adipose Tissue
Signal Transduction

Keywords

  • Adipocyte
  • Differentiation
  • Osteoblast
  • Protein phosphatase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

Reduction of protein phosphatase 2A Cα promotes in vivo bone formation and adipocyte differentiation. / Yoshida, Kaya; Teramachi, Jumpei; Uchibe, Kenta; Ikegame, Mika; Qiu, Lihong; Yang, Di; Okamura, Hirohiko.

In: Molecular and Cellular Endocrinology, 01.01.2017.

Research output: Contribution to journalArticle

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AU - Yoshida, Kaya

AU - Teramachi, Jumpei

AU - Uchibe, Kenta

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AU - Qiu, Lihong

AU - Yang, Di

AU - Okamura, Hirohiko

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