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J. Funct. Morphol. Kinesiol. 2017, 2(4), 41; https://doi.org/10.3390/jfmk2040041

TGF-β1-Dependent Downregulation of HDAC9 Inhibits Maturation of Human Osteoblasts

Siegfried Weller Institute for Trauma Research at the BG Trauma Center, Eberhard Karls Universität, D-72076 Tübingen, Germany
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Received: 18 October 2017 / Revised: 6 November 2017 / Accepted: 8 November 2017 / Published: 13 November 2017
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Abstract

Transforming growth factor β (TGF-β) is a key regulator of bone density. Recently, we have shown that TGF-β1 effectively blocks bone morphogenetic protein-induced maturation of human osteoblasts (hOBs) in a histone deacetylase (HDAC)-dependent manner. To better understand the underlying mechanisms and to identify possible therapeutic targets, the current study aimed at characterizing the expression changes of different HDACs in hOBs following recombinant human TGF-β1 treatment and investigating the effect of the altered HDACs on both the proliferation and maturation of hOBs and osteogenic cell lines. As expected from our previous work, exposure to rhTGF-β1 induced the expression of HDACs (HDAC1, -2, -3, -6). However, to our surprise, rhTGF-β1 treatment strongly suppressed the expression of HDAC9 during osteogenic differentiation. HDAC9 is reported to suppress osteoclastogenesis; however, little is known about the role of HDAC9 in osteogenesis. Chemical inhibition of HDAC9 with TMP269 increased cell numbers of hOBs, but significantly decreased their osteogenic function (alkaline phosphatase activity and matrix mineralization). In osteogenic cell lines (MG-63, CAL-72 and SAOS-2), the expression of HDAC9 negatively correlates with their proliferation capacity and positively correlates with their osteogenic differentiation potential. Being able to boost osteoclasts while inhibiting osteoblasts makes HDAC9 an interesting therapeutic target to support fracture healing and bone metabolisms. View Full-Text
Keywords: primary human osteoblasts (phOBs); transforming growth factor β1 (TGF-β1); histone deacetylase 9 (HDAC9) primary human osteoblasts (phOBs); transforming growth factor β1 (TGF-β1); histone deacetylase 9 (HDAC9)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Ehnert, S.; Heuberger, E.; Linnemann, C.; Nussler, A.K.; Pscherer, S. TGF-β1-Dependent Downregulation of HDAC9 Inhibits Maturation of Human Osteoblasts. J. Funct. Morphol. Kinesiol. 2017, 2, 41.

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J. Funct. Morphol. Kinesiol. EISSN 2411-5142 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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