Potential Role of BMP7 in Regenerative Dentistry.

In recent years, the field of regenerative dentistry has garnered considerable attention for its focus on restoring and renewing damaged dental tissue. This narrative review explores the potential of bone morphogenetic protein 7 (BMP7) and its diverse applications in the regeneration of dental tissue. Recently, significant efforts have been made to understand BMP7's role in advancing regenerative dentistry. Amongst the various signalling molecules investigated for their regenerative capabilities, BMP7 emerges as a pivotal candidate, demonstrating the ability to stimulate the regeneration of dental pulp, periodontal, craniofacial, and alveolar bone tissues for dental implant placement. Whilst BMP7 exhibits significant promise as a therapeutic agent in regenerative dentistry, further research and clinical trials are necessary to fully unlock its potential and optimise its clinical effectiveness in addressing diverse dental and craniofacial conditions. This review highlights BMP7's substantial potential and emphasises the ongoing need for continued research to effectively harness its clinical utility in diverse dental and craniofacial contexts.

Phytic acid effect on periodontal ligament fibroblast: An in-vitro study.

OBJECTIVES: This study evaluated phytic acid (IP6) effect on the viability, alkaline phosphatase (ALP) activity and calcium release of human periodontal ligament (HPDL) cells in optimal (OGL) and elevated glucose level (EGL) in cell culture media. MATERIALS AND METHODS: Cells were seeded in OGL (1000mg/L) or EGL (4500 mg/L) media. IP6 was added at 0.005%, 0.01% or 0.02% concentrations for 24 or 48h, and XTT assay was performed. Cell differentiation and calcium release in presence of 0.02% IP6 in OGL or EGL in non-osteogenic or osteogenic media were analyzed using ALP assay and alizarin red staining, respectively. RESULTS: In OGL, IP6 enhanced the viability of the cells at both exposure times (P<0.05). However, IP6 lowered the viability of the cells with the presence of EGL compared to the control at both exposure times, except for 0.02% IP6 which showed comparable viability to the control at 48 h. In OGL and EGL, ALP activity of the cells was not affected by the presence of IP6 in non-osteogenic media; however, in osteogenic media IP6 lowered the ALP activity. Meanwhile, calcium release was the highest with IP6 within osteogenic media of EGL. CONCLUSIONS: IP6 effects on the HPDL cells were dependent on IP6 concentration, time of exposure, glucose levels and the osteogenic condition of the media. CLINICAL RELEVANCE: This study gives insights on the potential therapeutic effect of IP6 as adjunctive periodontal therapy in patients with diabetes.

Inhibition of Silver Diamine Fluoride-induced Tooth Discoloration by Using Natural Antioxidant: In Vitro Study.

AIM: Silver diamine fluoride (SDF) is a well-known caries preventive aid capable of arresting carious lesions and preventing secondary caries formation. Despite having the caries prevention potential, the clinical use of SDF is limited due to the tooth discoloration caused by SDF. The objective of this study was to evaluate the efficiency of natural antioxidants to inhibit SDF-induced tooth discoloration. MATERIALS AND METHODS: A total of 32 bovine teeth were polished to create a 6 mm circular window on the middle 1/3 (for enamel) or on the cervical 1/3 (for dentin) of the labial surface. Specimens were treated either with SDF alone or SDF followed by ascorbic acid (AA)/alpha lipoic acid (ALA)/7th generation bonding materials. The color parameters Lightness (L*), Chroma (C*), and Hue (H*) of the tooth window were measured at pretreatment, 1-hour, 1-week, and 1-month posttreatment using a digital color chromometer. RESULTS: Repeated measure ANOVA showed a significant tooth color alteration at 1-hour posttreatment. The L* and H* values dropped and C* value elevated significantly in 1-hour posttreatment measurement. All experimental groups showed significant tooth color alteration after treatment (p < 0.05) and were unable to reverse the discoloration even after 1-month period except the ALA group which did not show any significant (p > 0.05) color alteration compared with the pretreatment value. CONCLUSIONS: Within the limitation of the in vitro model and according to the results of this study, it can be concluded that ALA has the potential to prevent SDF-induced tooth discoloration; however, AA was unable to prevent the discoloration. CLINICAL SIGNIFICANCE: SDF induces discoloration of enamel and dentin can be reversed by applying Alpha lipoic acid immediacy after SDF application.

Nicotinamide riboside kinase-2 alleviates ischemia-induced heart failure through P38 signaling.

Nicotinamide riboside kinase-2 (NRK-2), a muscle-specific ß1 integrin binding protein, predominantly expresses in skeletal muscle with a trace amount expressed in healthy cardiac tissue. NRK-2 expression dramatically increases in mouse and human ischemic heart however, the specific role of NRK-2 in the pathophysiology of ischemic cardiac diseases is unknown. We employed NRK2 knockout (KO) mice to identify the role of NRK-2 in ischemia-induced cardiac remodeling and dysfunction. Following myocardial infarction (MI), or sham surgeries, serial echocardiography was performed in the KO and littermate control mice. Cardiac contractile function rapidly declined and left ventricular interior dimension (LVID) was significantly increased in the ischemic KO vs. control mice at 2 weeks post-MI. An increase in mortality was observed in the KO vs. control group. The KO hearts displayed increased cardiac hypertrophy and heart failure reflected by morphometric analysis. Consistently, histological assessment revealed an extensive and thin scar and dilated LV chamber accompanied with elevated fibrosis in the KOs post-MI. Mechanistically, we observed that loss of NRK-2 enhanced p38α activation following ischemic injury. Consistently, ex vivo studies demonstrated that the gain of NRK-2 function suppresses the p38α as well as fibroblast activation (α-SMA expression) upon TGF-ß stimulation, and limits cardiomyocytes death upon hypoxia/re­oxygenation. Collectively our findings show, for the first time, that NRK-2 plays a critical role in heart failure progression following ischemic injury. NRK-2 deficiency promotes post-MI scar expansion, rapid LV chamber dilatation, cardiac dysfunction and fibrosis possibly due to increased p38α activation.

Osteogenesis imperfecta: new genes reveal novel mechanisms in bone dysplasia.

Osteogenesis imperfecta (OI) is a skeletal dysplasia characterized by fragile bones and short stature and known for its clinical and genetic heterogeneity which is now understood as a collagen-related disorder. During the last decade, research has made remarkable progress in identifying new OI-causing genes and beginning to understand the intertwined molecular and biochemical mechanisms of their gene products. Most cases of OI have dominant inheritance. Each new gene for recessive OI, and a recently identified gene for X-linked OI, has shed new light on its (often previously unsuspected) function in bone biology. Here, we summarize the literature that has contributed to our current understanding of the pathogenesis of OI.

Nck influences preosteoblastic/osteoblastic migration and bone mass.

Migration of the cells in osteoblastic lineage, including preosteoblasts and osteoblasts, has been postulated to influence bone formation. However, the molecular bases that link preosteoblastic/osteoblastic cell migration and bone formation are incompletely understood. Nck (noncatalytic region of tyrosine kinase; collectively referred to Nck1 and Nck2) is a member of the signaling adaptors that regulate cell migration and cytoskeletal structures, but its function in cells in the osteoblastic lineage is not known. Therefore, we examined the role of Nck in migration of these cells. Nck is expressed in preosteoblasts/osteoblasts, and its knockdown suppresses migration as well as cell spreading and attachment to substrates. In contrast, Nck1 overexpression enhances spreading and increases migration and attachment. As for signaling, Nck double knockdown suppresses migration toward IGF1 (insulin-like growth factor 1). In these cells, Nck1 binds to IRS-1 (insulin receptor substrate 1) based on immunoprecipitation experiments using anti-Nck and anti-IRS-1 antibodies. In vivo, Nck knockdown suppresses enlargement of the pellet of DiI-labeled preosteoblasts/osteoblasts placed in the calvarial defects. Genetic experiments indicate that conditional double deletion of both Nck1 and Nck2 specifically in osteoblasts causes osteopenia. In these mice, Nck double deficiency suppresses the levels of bone-formation parameters such as bone formation rate in vivo. Interestingly, bone-resorption parameters are not affected. Finally, Nck deficiency suppresses repair of bone injury after bone marrow ablation. These results reveal that Nck regulates preosteoblastic/osteoblastic migration and bone mass.

Nck1 deficiency accelerates unloading-induced bone loss.

Mechanical stress is an important signal to determine the levels of bone mass. Unloading-induced osteoporosis is a critical issue in bed-ridden patients and astronauts. Many molecules have been suggested to be involved in sensing mechanical stress in bone, though the mechanisms involved in this phenomenon are not fully understood. Nck1 is an adaptor protein known to mediate signaling from plasma membrane-activated receptors to cytosolic effectors regulating actin cytoskeleton remodeling. Nck1 has also been implicated in cellular responses to endoplasmic reticulum stress. In vitro, in case of cell stress the actin cytoskeleton is disrupted and in such cases Nck1 has been reported to enter the nucleus of the cells to mediate the nuclear actin polymerization. However, the role of Nck1 in vivo during the bone response to mechanical stimuli is unknown. The purpose of this study is to examine the role of Nck1 in unloading-induced bone loss in vivo. Sciatic and femoral nerve resection was conducted. Neurectomy-based unloading enhanced Nck1 gene expression in bone about twofold. Using the Nck1 deficient mice and control Nck1+/+, effects of neurectomy-based unloading on bone structure were examined. Unloading reduced bone volume in wild type mice by 30% whereas the levels in bone loss were exacerbated to 50% in Nck1 deficient mice due to neurectomy after 4 weeks. These data demonstrate that Nck1 gene deficiency accelerates the mechanical unloading-induced bone loss suggesting Nck1 to be a crucial molecule in mechanical stress mediated regulation in bone metabolism.