PMID- 20681807 OWN - NLM STAT- MEDLINE DCOM- 20110224 LR - 20101102 IS - 1943-3670 (Electronic) IS - 0022-3492 (Linking) VI - 81 IP - 11 DP - 2010 Nov TI - Bone morphogenetic protein-7 enhances cementoblast function in vitro. PG - 1663-74 LID - 10.1902/jop.2010.100074 [doi] AB - BACKGROUND: Bone morphogenetic protein (BMP)-7 is a potent bone-inducing factor and was shown to promote periodontal regeneration in vivo and in vitro; however, to our knowledge, the specific effect of BMP-7 on cementoblasts has not been defined. We aimed to investigate the effects of BMP-7 on cementoblasts, which are cells responsible for tooth root-cementum formation. We hypothesized that BMP-7 would regulate mineralized tissue-associated genes in cementoblasts and influence the expression profile of genes associated with cementoblast extracellular matrix (ECM) and cell adhesion molecules (CAMs). METHODS: A murine immortalized cementoblast cell line (OCCM.30) was cultured with and without 50 ng/ml BMP-7. After 72 hours, total RNA was isolated, and mRNA levels for bone/cementum markers, including bone sialoprotein (BSP), osteocalcin (OCN), osteopontin (OPN), and runt-related transcription factor-2 (Runx2), were investigated by real-time quantitative reverse transcription-polymerase chain reaction (Q-PCR). In vitro mineral nodule formation was assayed on day 8 using von Kossa staining. A pathway-specific gene-expression array was used to determine BMP-7-responsive ECM and CAM genes in cementoblasts. RESULTS: Mineralized tissue markers were strongly regulated by BMP-7, with an almost three-fold increase in BSP and OCN transcripts and significant increases in OPN and Runx2 mRNA expressions. BMP-7 treatment markedly stimulated cementoblast-mediated biomineralization in vitro compared to untreated cells at day 8. BMP-7 treatment altered the OCCM.30 expression profile for ECM and CAM functional gene groups. BMP-7 tended to increase the expression of collagens and matrix metalloproteinases (MMPs), mildly decreased tissue inhibitors of MMPs (TIMPs), and had mixed regulatory effects on integrins. Using Q-PCR, selected array results were confirmed, including a significant BMP-7-induced increase in MMP-3 and a decrease in TIMP-2 mRNA expression. CONCLUSION: These results support the promising applications of BMP-7 in therapies aimed at regenerating periodontal tissues lost as a consequence of disease. FAU - Hakki, Sema S AU - Hakki SS AD - Department of Periodontology, Faculty of Dentistry, Selcuk University, Konya, Turkey. sshakki@yahoo.com FAU - Foster, Brian L AU - Foster BL FAU - Nagatomo, Kanako J AU - Nagatomo KJ FAU - Bozkurt, S Buket AU - Bozkurt SB FAU - Hakki, Erdogan E AU - Hakki EE FAU - Somerman, Martha J AU - Somerman MJ FAU - Nohutcu, Rahime M AU - Nohutcu RM LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100803 PL - United States TA - J Periodontol JT - Journal of periodontology JID - 8000345 RN - 0 (Bone Morphogenetic Protein 7) RN - 0 (Cell Adhesion Molecules) RN - 0 (Core Binding Factor Alpha 1 Subunit) RN - 0 (Extracellular Matrix Proteins) RN - 0 (Integrins) RN - 0 (Runx2 protein, mouse) RN - 0 (Spp1 protein, mouse) RN - 0 (Tissue Inhibitor of Metalloproteinases) RN - 0 (bmp7 protein, mouse) RN - 104982-03-8 (Osteocalcin) RN - 106441-73-0 (Osteopontin) RN - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2) RN - 9007-34-5 (Collagen) RN - EC 3.4.24.- (Matrix Metalloproteinases) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.4.24.17 (Mmp3 protein, mouse) SB - IM MH - Animals MH - Bone Morphogenetic Protein 7/*pharmacology MH - Calcification, Physiologic/drug effects MH - Cell Adhesion Molecules/drug effects MH - Cell Differentiation/drug effects MH - Cell Line MH - Collagen/drug effects MH - Core Binding Factor Alpha 1 Subunit/drug effects MH - Dental Cementum/cytology/*drug effects MH - Extracellular Matrix Proteins/drug effects MH - Gene Expression Profiling MH - Gene Expression Regulation/drug effects MH - Integrins/drug effects MH - Matrix Metalloproteinase 3/drug effects MH - Matrix Metalloproteinases/drug effects MH - Mice MH - Osteocalcin/drug effects MH - Osteopontin/drug effects MH - Protein Array Analysis MH - Time Factors MH - Tissue Inhibitor of Metalloproteinase-2/drug effects MH - Tissue Inhibitor of Metalloproteinases/drug effects MH - Tooth Root/cytology/drug effects MH - Up-Regulation EDAT- 2010/08/05 06:00 MHDA- 2011/02/25 06:00 CRDT- 2010/08/05 06:00 PHST- 2010/08/05 06:00 [entrez] PHST- 2010/08/05 06:00 [pubmed] PHST- 2011/02/25 06:00 [medline] AID - 10.1902/jop.2010.100074 [doi] PST - ppublish SO - J Periodontol. 2010 Nov;81(11):1663-74. doi: 10.1902/jop.2010.100074. Epub 2010 Aug 3.