In concordance with the effect on damaged articular cartilage, CCN2 promotes the bone regeneration up to the exactly desired level without inducing any overgrowth. In these cases, the boundary of the original cortical tissue and the regenerated one at the defect site is almost invisible by histological observation [13]. The property of CCN2 to enhance the healing potential of bone tissue in a harmonized manner is of course ascribable to the molecular action of this protein as a CCN family member. In clinical dentistry, alveolar bone regeneration is a critical issue for the efficient support of dentures and stable fixation of dental implants for rigid

prosthesis. Neratinib datasheet With BMP-2, for example, nowadays it is not difficult to manufacture bone on the alveolar arch or at the bottom of a sinus. Nevertheless, clinicians sometimes face difficulty in the

maintenance of the added bone against subsequent resorption [65]. Considering its molecular nature, CCN2 may be more effective in keeping the engineered bone in a desired form as a coordinator of bone remodeling. Since CCN2 is a central mediator of fibrotic disorders, therapeutic approach targeting CCN2 in controlling fibrosis in every relevant organ ought to be explored in the future. In the tissues present deep inside of the body, such as the heart, kidneys and liver, a highly sophisticated drug delivery system is indispensable to specifically target CCN2 in these organs with agents that regulate its gene expression or modify its molecular behavior. In contrast, the oral cavity and skin are relatively easy to access without GDC0068 specific device for targeted delivery. Therefore, the anti-CCN2 strategy against skin dermal and gingival fibrosis is currently actively explored. Molecular therapy targeting CCN2 is being developed against drug-induced gingival triclocarban fibrosis, since removal of etiological factors is difficult in those cases [56]. A recent report has indicated that activation of Smad7, a repressive mediator of intracellular signal transduction, in gingival fibroblasts is effective in preventing the CCN2 induction and fibroblast/myofibroblast transition that cause gingival fibrosis

[66]. However, selective activation of Smad7 inside the cells by an extracellular approach appears difficult at present. Another report has described that nifedipine-induced gingival fibrosis that is mediated by CCN2 in concert with androgen receptors can be inhibited by flutamide, a non-steroidal receptor antagonist of androgens [67]. Regulation of CCN2 gene expression by direct administration of antisense oligonucleotides is being attempted as well in vivo. According to a recent study, injection of an anti-CCN2 modified oligonucleotide into skin wounds represses scar formation without affecting the proper wound healing process [68]. As such, development of novel strategies to down-regulate CCN2 is desired and is actually underway to control gingival fibrosis.