Abnormal profiles of cathepsin C secreted in urine of Papillon Lefevre syndrome patients.

BACKGROUND: Papillon Lefevre syndrome (PLS) is an autosomal recessive disorder that results from a mutated gene that encodes a lysosomal peptidase known as cathepsin C (CTSC). The clinical presentation of PLS involves mainly palmoplantar keratosis and periodontitis with a variable degree of severity. SUBJECTS: and methods: Our study included ten patients with a broad spectrum of palmoplantar keratosis and periodontitis severity. CTSC variants were detected by Sanger sequencing. CTSC protein secreted in urine was detected by western blotting. RESULTS: Five patients have missense variants, Four have nonsense variants, and one has splice variants in CTSC. The activation products of cathepsin C protein (Heavy and light chains) were absent in all patients' urine samples except one with a significantly reduced level compared to the controls. The dimeric form of CTSC protein was found in all the studied cases. The monomeric form was found in five cases. The products of proteolytic activation of CTSC by other cathepsins (L and S) were found in the urine samples of five of the patients. Each patient had a characteristic pattern of accumulated CTSC protein maturation/activation substrates, intermediates, and products. 40% of the patients had the activation products of other lysosomal cathepsins. CONCLUSION: Urinary CTSC in PLS patients could be used as a diagnostic biomarker for the biochemical screening of the disease. Different variants in CTSC result in different profiles of CTSC secreted in the urine of PLS patients. The profiles of secreted CTSC in urine could be correlated to the severity of palmoplantar keratosis.

Oral rehabilitation of a case with regional odontodysplasia using a regenerative approach-A case report and a review of literature.

AIM: to investigate for the first time whether the regenerative approach can be used to rehabilitate a case with regional odontodysplasia (ROD). ROD is a rare, localized developmental anomaly of the dental tissues. Moreover, we review the various treatment protocols for ROD and compare them to the suggested regenerative protocol. CASE REPORT: A 22-year-old female patient diagnosed with ROD in the upper left quadrant was presented to our clinic. Initially, the affected teeth were extracted and three implants were inserted. A combination of autologous bone marrow mononuclear cells (BMMNCs) seeded on a collagen sponge, nanohydroxyapatite, and autologous platelet-rich fibrin (PRF) was used to enhance bone regeneration in the defective area and around the inserted implants. After 9 months, bone regeneration and successful osteointegration around the inserted implants were achieved, permitting the insertion of a fourth implant. After an additional six months, a final fixed restoration was constructed. CONCLUSION: The suggested regenerative approach provides a better treatment option for ROD patients to regenerate the lost bone, rehabilitate aesthetics, and restore normal function.

The effects of hypoxia on the stemness properties of human dental pulp stem cells (DPSCs).

Recent studies have demonstrated that culture under hypoxia has beneficial effects on mesenchymal stem cells (MSCs). However, there are limitations to achieving a stable condition in conventional hypoxic CO2 incubators. DPSCs are a unique type of MSCs which are promising in many regenerative therapies. In this study, we investigated the ideal hypoxic culture environment for DPSCs using a new system that can provide controlled O2 environment. The effects of hypoxia (3%, 5%) on the stemness properties of DPSCs. Their morphology, proliferation rate, expression of stem cell markers, migration ability, mRNA expression of angiogenic/neurotrophic factors and immunomodulatory genes were evaluated and compared. Additionally, the effect of the discrete secretome on proliferation, migration, and neurogenic induction was assessed. Hypoxic DPSCs were found to be smaller in size and exhibited larger nuclei. 5% O2 significantly increased the proliferation rate, migration ability, expression of stem cell markers (CXCR4 and G-CSFR), and expression of SOX2, VEGF, NGF, and BDNF genes of DPSCs. Moreover, secretome collected from 5%O2 cultures displayed higher stimulatory effects on proliferation and migration of NIH3T3 cells and on neuronal differentiation of SH-SY5Y cells. These results demonstrate that 5%O2 may be ideal for enhancing DPSCs growth, stem cell properties, and secretome trophic effect.

Therapeutic Potential of Dental Pulp Stem Cell Secretome for Alzheimer's Disease Treatment: An In Vitro Study.

The secretome obtained from stem cell cultures contains an array of neurotrophic factors and cytokines that might have the potential to treat neurodegenerative conditions. Alzheimer's disease (AD) is one of the most common human late onset and sporadic neurodegenerative disorders. Here, we investigated the therapeutic potential of secretome derived from dental pulp stem cells (DPSCs) to reduce cytotoxicity and apoptosis caused by amyloid beta (Aß) peptide. We determined whether DPSCs can secrete the Aß-degrading enzyme, neprilysin (NEP), and evaluated the effects of NEP expression in vitro by quantitating Aß-degrading activity. The results showed that DPSC secretome contains higher concentrations of VEGF, Fractalkine, RANTES, MCP-1, and GM-CSF compared to those of bone marrow and adipose stem cells. Moreover, treatment with DPSC secretome significantly decreased the cytotoxicity of Aß peptide by increasing cell viability compared to nontreated cells. In addition, DPSC secretome stimulated the endogenous survival factor Bcl-2 and decreased the apoptotic regulator Bax. Furthermore, neprilysin enzyme was detected in DPSC secretome and succeeded in degrading Aß 1-42 in vitro in 12 hours. In conclusion, our study demonstrates that DPSCs may serve as a promising source for secretome-based treatment of Alzheimer's disease.