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TGF-β1-Dependent Downregulation of HDAC9 Inhibits Maturation of Human Osteoblasts
- Source :
- Journal of Functional Morphology and Kinesiology; Volume 2; Issue 4; Pages: 41, Journal of Functional Morphology and Kinesiology, Vol 2, Iss 4, p 41 (2017)
- Publication Year :
- 2017
- Publisher :
- MDPI AG, 2017.
-
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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
lcsh:Diseases of the musculoskeletal system
Histology
primary human osteoblasts (phOBs)
Cell
Physical Therapy, Sports Therapy and Rehabilitation
Bone healing
Biology
03 medical and health sciences
Rheumatology
Downregulation and upregulation
Internal medicine
medicine
Orthopedics and Sports Medicine
transforming growth factor β1 (TGF-β1)
histone deacetylase 9 (HDAC9)
HDAC9
HDAC1
Cell biology
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Alkaline phosphatase
Histone deacetylase
lcsh:RC925-935
Anatomy
Transforming growth factor
Subjects
Details
- ISSN :
- 24115142
- Volume :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of Functional Morphology and Kinesiology
- Accession number :
- edsair.doi.dedup.....1d5ecf1c3d44f9f3da5a2eeeea1a8aaa