Modulation of the resorption and osteoconductivity of alpha-calcium sulfate by histone deacetylase inhibitors.
Calcium sulfate (CS) is an osteoconductive material with a long history of clinical use. However, its resorptive properties are not optimal for bone regeneration. Recently, histone deacetylase inhibitors (HDIs) have been suggested as bone regeneration tools. In this study, we investigated the effects of the HDIs sodium butyrate and trichostatin A on alpha-form CS (alphaCS) performance. MC3T3-E1 pre-osteoblasts cultured on alphaCS containing either HDI (alphaCS/HDI) showed higher levels of alkaline phosphatase activity than those cultured on alphaCS alone. The expression of genes characteristic of the osteoblast phenotype, including Runx2, osteocalcin, and bone sialoprotein, was strongly promoted by alphaCS/HDI. When cultured on alphaCS/HDIs, the osteoclastic differentiation of RAW264.7 monocytes was substantially suppressed, as measured by tartrate-resistant acid phosphatase (TRAP) activity and the expression levels of calcitonin receptor and TRAP. Neither HDI affected the CS setting time, compressive strength, or dissolution in a simulated body fluid. In a rat calvarial model of critical size bone defects, alphaCS/HDIs enhanced osteoblast differentiation, led to new bone formation, and delayed resorption, as confirmed by micro-computed tomography and histological analyses.
Department of Cell & Developmental Biology, Dental Research Institute and BK21 Program, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
Hong-Moon
HM
Jung
Gin-Ah
GA
Song
Yong-Keun
YK
Lee
Jeong-Hwa
JH
Baek
Hyun-Mo
HM
Ryoo
Gwan-Shik
GS
Kim
Phil-Hoon
PH
Choung
Kyung Mi
KM
Woo
D016475:3T3 Cells; D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002133:Calcium Sulfate / Q000378:metabolism*; D002460:Cell Line; D017931:DNA Primers; D015870:Gene Expression; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D051381:Rats; D000071681:Tartrate-Resistant Acid Phosphatase
D017931:DNA Primers; D056572:Histone Deacetylase Inhibitors; D007527:Isoenzymes; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D002133:Calcium Sulfate