Combined effects of dentin sialoprotein and bone morphogenetic protein-2 on differentiation in human cementoblasts

Lee, So-Youn; Auh, Q-Schick; Kang, Soo-Kyung; Kim, Hyung-Joon; Lee, Jung-Woo; Noh, Kwantae; Jang, Jun-Hyeog; Kim, Eun-Cheol
July 2014
Cell & Tissue Research;Jul2014, Vol. 357 Issue 1, p119
Academic Journal
The aim of this study is to determine the effects of the combination of recombinant human BMP-2 (rh-BMP-2) and dentin sialoprotein (rh-DSP) on growth and differentiation in human cementoblasts and determine the underlying signal transduction mechanism. Compared to treatment of cementoblasts with either rh-BMP-2 or rh-DSP alone, the combination of rh-BMP-2 and rh-DSP synergistically increased cell growth, ALP activity, nodule formation and expression of differentiation markers. The differentiation-promoting effect was also observed in periodontal ligament cells and an osteoblastic cell line. Likewise, combination of rh-DSP and rh-BMP-2 increased BMP-2 mRNA expression and Smad1/5/8 phosphorylation, which was blocked by the BMP antagonist noggin. The expression levels of α2β1 integrin and RhoA, as well as the phosphorylation status of FAK and Akt, were increased by the combination of rh-BMP-2 and rh-DSP in a time-dependent manner. In addition, rh-BMP-2 and rh-DSP enhanced expression of Wnt ligands, β-catenin activation and GSK-3β phosphorylation, all of which were inhibited by the Wnt receptor antagonist DKK1. Furthermore, treatment with rh-DSP plus rh-BMP-2 resulted in phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 and also induced the nuclear translocation of the NF-κB p65 subunit, which was blocked by noggin. This study demonstrates for the first time that rh-DSP and rh-BMP-2 act synergistically, enhancing each other's ability to stimulate cementoblastic cell growth and differentiation in vitro via autocrine BMP, integrin, Wnt/β-catenin, MAP kinase and NF-κB pathways. These results support the therapeutic potential of a combination strategy for aiding periodontal regeneration.


Related Articles

  • BMP9 signaling in stem cell differentiation and osteogenesis. Lamplot, Joseph D.; Jiaqiang Qin; Guoxin Nan; Jinhua Wang; Xing Liu; Liangjun Yin; Tomal, Justin; Ruidong Li; Wei Shui; Hongyu Zhang; Kim, Stephanie H.; Wenwen Zhang; Jiye Zhang; Yuhan Kong; Denduluri, Sahitya; Rogers, Mary Rose; Pratt, Abdullah; Haydon, Rex C.; Luu, Hue H.; Angeles, Jovito // American Journal of Stem Cells;2013, Vol. 2 Issue 1, p1 

    Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily and play a critical role in skeletal development, bone formation and stem cell differentiation. Disruptions in BMP signaling result in a variety of skeletal and extraskeletal anomalies. BMP9 is a poorly characterized...

  • BMP-2 decreases Mash1 stability by increasing Id1 expression. Viñals, Francesc; Reiriz, Julia; Ambrosio, Santiago; Bartrons, Ramon; Rosa, Jose Luis; Ventura, Francesc // EMBO Journal;9/1/2004, Vol. 23 Issue 17, p3527 

    In neural development, bone morphogenetic proteins (BMPs) restrict neuronal differentiation, thereby promoting the maintenance of progenitor cells or even inducing astrocytogenesis. We report that exposure of neuroendocrine lung carcinoma cells to BMP-2 leads to a rapid decline in steady-state...

  • Osteogenic Differentiation of MSC through Calcium Signaling Activation: Transcriptomics and Functional Analysis. Viti, Federica; Landini, Martina; Mezzelani, Alessandra; Petecchia, Loredana; Milanesi, Luciano; Scaglione, Silvia // PLoS ONE;2/1/2016, Vol. 11 Issue 2, p1 

    The culture of progenitor mesenchymal stem cells (MSC) onto osteoconductive materials to induce a proper osteogenic differentiation and mineralized matrix regeneration represents a promising and widely diffused experimental approach for tissue-engineering (TE) applications in orthopaedics. Among...

  • Increased Osteogenic Differentiation of Periodontal Ligament Stem Cells on Polydopamine Film Occurs via Activation of Integrin and PI3K Signaling Pathways. Lee, Jeong Seok; Yi, Jin-Kyu; an, Seong Yeong; Heo, Jung Sun // Cellular Physiology & Biochemistry (Karger AG);Nov2014, Vol. 34 Issue 5, p1824 

    Background/Aims: Mussel-inspired polydopamine (PDA) is known to be an effective bioadhesive and bioactive material for controlling stem cell fate, which is important in stem cell-based regenerative medicine; however, the effect of PDA on osteogenic differentiation of periodontal ligament stem...

  • BMP-2 Induced Expression of Alx3 That Is a Positive Regulator of Osteoblast Differentiation. Matsumoto, Takashi; Yamada, Atsushi; Aizawa, Ryo; Suzuki, Dai; Tsukasaki, Masayuki; Suzuki, Wataru; Nakayama, Mutsuko; Maki, Koutaro; Yamamoto, Matsuo; Baba, Kazuyoshi; Kamijo, Ryutaro // PLoS ONE;Jun2013, Vol. 8 Issue 6, p1 

    Bone morphogenetic proteins (BMPs) regulate many aspects of skeletal development, including osteoblast and chondrocyte differentiation, cartilage and bone formation, and cranial and limb development. Among them, BMP-2, one of the most potent osteogenic signaling molecules, stimulates osteoblast...

  • Inhibition of Bone Morphogenetic Protein Signal Transduction Prevents the Medial Vascular Calcification Associated with Matrix Gla Protein Deficiency. Malhotra, Rajeev; Burke, Megan F.; Martyn, Trejeeve; Shakartzi, Hannah R.; Thayer, Timothy E.; O’Rourke, Caitlin; Li, Pingcheng; Derwall, Matthias; Spagnolli, Ester; Kolodziej, Starsha A.; Hoeft, Konrad; Mayeur, Claire; Jiramongkolchai, Pawina; Kumar, Ravindra; Buys, Emmanuel S.; Yu, Paul B.; Bloch, Kenneth D.; Bloch, Donald B. // PLoS ONE;Jan2015, Vol. 10 Issue 1, p1 

    Objective: Matrix Gla protein (MGP) is reported to inhibit bone morphogenetic protein (BMP) signal transduction. MGP deficiency is associated with medial calcification of the arterial wall, in a process that involves both osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs)...

  • Zirconium Ions Up-Regulate the BMP/SMAD Signaling Pathway and Promote the Proliferation and Differentiation of Human Osteoblasts. Chen, Yongjuan; Roohani-Esfahani, Seyed-Iman; Lu, ZuFu; Zreiqat, Hala; Dunstan, Colin R. // PLoS ONE;Jan2015, Vol. 10 Issue 1, p1 

    Zirconium (Zr) is an element commonly used in dental and orthopedic implants either as zirconia (ZrO2) or in metal alloys. It can also be incorporated into calcium silicate-based ceramics. However, the effects of in vitro culture of human osteoblasts (HOBs) with soluble ionic forms of Zr have...

  • BMP Pathway Regulation of and by Macrophages. Talati, Megha; West, James; Zaynagetdinov, Rinat; Hong, Charles C.; Han, Wei; Blackwell, Tom; Robinson, Linda; Blackwell, Timothy S.; Lane, Kirk // PLoS ONE;Apr2014, Vol. 9 Issue 4, p1 

    Pulmonary arterial hypertension (PAH) is a disease of progressively increasing pulmonary vascular resistance, associated with mutations of the type 2 receptor for the BMP pathway, BMPR2. The canonical signaling pathway for BMPR2 is through the SMAD family of transcription factors. BMPR2 is...

  • Effect of miR-20b on Apoptosis, Differentiation, the BMP Signaling Pathway and Mitochondrial Function in the P19 Cell Model of Cardiac Differentiation In Vitro. Zhu, Shasha; Hu, Xiaoshan; Yu, Zhangbin; Peng, Yuzhu; Zhu, Jingai; Liu, Xuehua; Li, Mengmeng; Han, Shuping; Zhu, Chun // PLoS ONE;Apr2015, Vol. 10 Issue 4, p1 

    Objective: To explore the effect of miR-20b on apoptosis, differentiation, the BMP signaling pathway and mitochondrial function in the P19 cell model of cardiac differentiation in vitro. Methods: A miR-20b over-expression vector, a miR-20b silencing vector and their corresponding empty vectors...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics