|Year : 2015 | Volume
| Issue : 1 | Page : 10-13
Osterix combined with gene-activated matrix: A potential integrated strategy for achieving cementum regeneration
Rubing Liu1, Zhengguo Cao2
1 Department of Periodontology, The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST KLOS) and Key Laboratory for Oral Biomedical Engineering of Ministry of Education; Department of Periodontology, the Affiliated Hospital of Stomatology, College of Medicine, Zhejiang University, Hangzhou, China
2 Department of Periodontology, The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST KLOS) and Key Laboratory for Oral Biomedical Engineering of Ministry of Education; Department of Periodontology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
|Date of Web Publication||5-Feb-2015|
Department of Periodontology, School and Hospital of Stomatology, Wuhan University, Wuhan
Source of Support: None, Conflict of Interest: None
Introduction: Human periodontitis is the most common infectious disease that results in the destruction of periodontal supporting tissues including the root cementum. Currently cementum regeneration, as a vital event, is considered as a gold standard of successful periodontal tissue reconstruction. Nevertheless, one of the important requirements of cementum reestablishment is the recruitment and differentiation of pre-cementoblasts into functional cementoblasts, which requires effective regulator factors. Recently, Osterix (Osx) is known to be a key transcriptional factor essential for osteogenesis and especially for cementogenesis. Although there are various interesting approaches involving tissue engineering, gene-activated matrix (GAM) is one of the most promising approaches to achieve reliable restoration of the periodontium. The Hypothesis: Based on the recent advances in understanding the mechanisms of Osx in cementum development and formation, we hypothesize that Osx plays a critical role in periodontal regeneration and Osx combined with GAM may be an effective strategy for the regeneration of cementum. Evaluation of the Hypothesis: Osx combined with GAM could pave the way for the development of new tissue engineering procedures and have the potential to play a pivotal role in cementum regeneration, eventually increasing the predictability of periodontal tissue regeneration.
Keywords: Cementogenesis, gene-activated matrix, osterix, periodontal tissue engineering
|How to cite this article:|
Liu R, Cao Z. Osterix combined with gene-activated matrix: A potential integrated strategy for achieving cementum regeneration. Dent Hypotheses 2015;6:10-3
| Introduction|| |
Human periodontitis is a common infectious disease and contributes to the destruction of periodontal supporting tissues including the cementum and ultimately leads to tooth loss if it is not adequately treated.  Currently, periodontal tissue engineering is an emerging multidisciplinary field and can be advanced by the gene-activated matrix (GAM) technology which combines tissue engineering and gene delivery system strategies. ,,, It is well known that the gold standard of periodontal regeneration is functional cementum reestablishment.  The regeneration of cementum contains many events,  including the migration and attachment of cementoblasts to the appointed position, proliferation and differentiation of cells, matrix biosynthesis and mineralization. All these require numerous growth factors and transcriptional factors including Osterix (Osx). ,
Essential role of Osx in bone formation and cementogenesis, as an important transcriptional factor
Osx, also named Sp7, is a transcriptional factor for osteoblast differentiation and participates in mineralization. ,, In 2002, Osx was firstly identified as a bone morphogenetic protein-2 inducible gene in the mice C2C12 skeletal muscle cells.  Osx acts as a downstream gene of Runx2. ,, During bone formation, osteoblast differentiation from mesenchymal stem cells occurs through a multistep molecular pathway regulated by various signaling proteins and transcriptional factors, including Ihh, Wnt, and FGF families as well as Pax, Hox, bHLH, Runx2, and Osx, which outline the three-dimensional information that determines the shape of mesenchymal condensations. ,
Osx is required for osteoblast differentiation. It has been demonstrated that Osx is essential for osteoblast differentiation in vivo and vitro,,, as well as in embryos  and postnatal mice.  During the process of osteogenesis, there are several bone related genes which are responsible for the deposition and maturation of bone extracellular matrix, such as BSP, OCN, OPN, and ALP. ,,, In Osx null mutant embryos, which die at birth, no bone formation takes place in the endochondral membranous skeleton. Those bone related genes are all absent in the condensed mesenchyme of membranous and endochondral skeletal elements.  Therefore we conclude that Osx promotes the differentiation of osteoblasts.
Runx2 and Osx were co-localized in cementoblasts, and Osx was significantly upregulated in cementum on both compression and tension sides during the orthodontic tooth movement. , Specifically, our recent studies showed that there is a close relationship between a temporal- and spatial-expression pattern of Osx and formation of cellular cementum, and an accelerated cementum formation in the 3.6-Col 1-Osx transgenic mouse line. On the other hand, conditional deletion of Osx in mesenchymal cells by crossing the 2.3 kb Col 1-Cre and Osx loxP mice led to a sharp reduction in cellular cementum formation (including cementum mass and mineral deposition rate),  suggesting that Osx may be required for cementoblasts differentiation. Jin et al., conducted cementum engineering with cloned cementoblasts (OCCMs) combined with three-dimensional poly lactic-co-glycolic acid (PLGA) scaffolds and detected the gene expression of type I collagen, OCN, and BSP in OCCM-seeded PLGA scaffolds. Furthermore, when cementoblasts were transiently transfected with PEX3-Osterix plasmid, significantly higher transcript level of BSP, OCN, and ALP was observed. So we can confirm that Osx does exist and functionally operate in cementogenesis.
| The Hypothesis|| |
Human periodontitis would often result in tooth loss ultimately, if there were no adequate and effective treatments. This tragedy will undoubtedly exert significant impact on the patient's quality of life. Hope is, as expected, pinned on periodontal tissue engineering with the help of gene-activated matrix (GAM) technology. Furthermore, emerging reports have demonstrated the express of osteogenic transcriptional factor Osx and its vital function in cementogenesis. ,, Based on the common characteristics between cementum and bone as well as the recent advances of osterix in cementum formation, we make the following hypothesis.
Possible role of Osx in cementum regeneration
Although cementum differs from bone in its histological profile by lacking innervation and vascularization, and has limited remodeling potential, it is very similar to bone. Cementum seems to contain elements in common with those associated with bone and be developmentally controlled by similar factors.  These factors may regulate differentiation and proliferation of cementoblasts and deposition of cementum matrix. Cementum is consisted of approximately 50% hydroxyapatite and 50% collagen and non-collagenous proteins.  We have also discussed the existence of Osx in cementum and its potential role in cementum development via controlling the proliferation and differentiation of cementoblasts. As it is known, the process of tissue engineering is imitating that of embryogenesis and morphogenesis involved in the original formation of the tissue. Moreover, in a tissue engineering biology model, bone regeneration is driven by transcriptional factors Osx, which responds to released BMP2.  So Osx may play a positive role in periodontal tissue engineering.
The key event in periodontal tissue regeneration is the attachment of connective tissue fibers (Sharpey's fibers) to the hard tissues (bone and cementum).  Cementoblasts are responsible for laying down cementum on the root surface. It is clear that types I collagen, OCN, and BSP are essential for cementum mineralization ,, and are able to be upregulated by Osx,  so the process of cementum regeneration maybe impossibly occur without the Osx. And for this reason, we postulated that Osx might play a potential role in cementoblasts differentiation and serve as a possible positive regulator for matrix mineralization in the process of cementum reconstruction.
Osterix combined with GAM: A potential integrated strategy for achieving cementum regeneration
Recently, more attention has been paid to gene-activated matrix (GAM) in periodontal tissue regeneration. A novel GAM with embedded chitosan/plasmid nanoparticles encoding PDGF based on porous chitosan/collagen composite scaffold has been developed. This scaffold provides a non-viral vector to condense DNA and serves as an effective kind of material for PDLCs adherence and proliferation.  On the other hand, the DNA can also be encapsulated by cationic liposome  to form lipoplexes, which is capable to locally express the relevant regulatory factors in the process of periodontal regeneration. The feasible combination of effective Osx and liposome or scaffold material indicates that the novel GAM strategy with Osx has a promising role in the application of periodontal tissue regeneration, especially in the reconstruction of cementum.
| Evaluation of the Hypothesis|| |
It is obvious that significant progress has occurred in the field of periodontal tissue engineering at the preclinical level during the past decades. Meanwhile, the study of signaling pathway associated with the proliferation and differentiation of cementoblasts is and will always be the hot topic among researchers and will lead to the generation of new knowledge about cementum regeneration. Undoubtedly Osx, as a potential factor in development and regeneration of cementum, will pave the way for the development of new tissue engineering procedures needed for the predictable regeneration of periodontal tissues. Taken together, we believe Osx combined with GAM could actually play a pivotal role in cementum and the other periodontal tissue regeneration methods including alveolar bone and periodontal ligament, and eventually improves the quality of life of patients.
| Acknowledgements|| |
The study has been supported by grants from the National Natural Science Foundation of China (81170933 to ZC). All the authors don't have any conflict of interest.
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