Proteomic Profiling of the First Human Dental Pulp Mesenchymal Stem/Stromal Cells from Carbonic Anhydrase II Deficiency Osteopetrosis Patients

Abstract

Osteopetrosis is a hereditary disorder characterized by sclerotic, thick, weak, and brittle bone. The biological behavior of mesenchymal cells obtained from osteopetrosis patients has not been well-studied. Isolated mesenchymal stem/stromal cells from dental pulp (DP-MSSCs) of recently extracted deciduous teeth from osteopetrosis (OP) patients and healthy controls (HCs) were compared. We evaluated whether the dental pulp of OP patients has a population of MSSCs with similar multilineage differentiation capability to DP-MSSCs of healthy subjects. Stem/progenitor cells were characterized using immunohistochemistry, flow cytometry, and proteomics. Our DP-MSSCs were strongly positive for CD44, CD73, CD105, and CD90. DP-MSSCs obtained from HC subjects and OP patients showed similar patterns of proliferation and differentiation as well as gene expression. Proteomic analysis identified 1499 unique proteins with 94.3% similarity in global protein fingerprints of HCs and OP patients. Interestingly, we observed subtle differences in expressed proteins of osteopetrosis disease-related in pathways, including MAPK, ERK 1/2, PI3K, and integrin, rather than in the stem cell signaling network. Our findings of similar protein expression signatures in DP-MSSCs of HC and OP patients are of paramount interest, and further in vivo validation study is needed. There is the possibility that OP patients could have their exfoliating deciduous teeth banked for future use in regenerative dentistry.

Fluconazole-Induced Protein Changes in Osteogenic and Immune Metabolic Pathways of Dental Pulp Mesenchymal Stem Cells of Osteopetrosis Patients

“…We previously reported that the dental pulp of OP patients contains a population of mesenchymal stem/stromal cells (MSSCs) capable of multilineage differentiation comparable to that of healthy subjects’ DP-MSSCs [ 8 ]. Our isolated DP-MSSCs were shown to be CD44-, CD73-, CD105- and CD90-positive by immunohistochemistry and flow cytometry analysis.…”

“…High bone density on radiographs is a common symptom of this condition, first recognized in 1904 by the German radiologist Albers-Schonberg [ 7 ]. This most noticeable sign of increased bone density on radiographs is caused by low osteoclast activity, which reduces bone resorption [ 8 , 9 ]. Instead of conferring strength, the overly dense bone architecture leads to brittleness, which predisposes to fracture and subsequent infections.…”

“…Analytical proteomics has shown promise as a method for discovering protein biomarkers for a variety of diseases, but only a small portion of this research has been translated into clinical practice. Recent work by our lab showed a global protein analysis of stromal cells and mesenchymal stem cells isolated from the dental pulps of patients with osteopetrosis who were also deficient in CAII [ 8 ]. Inhibitors of CA have been the subject of extensive research in the past and present due to the therapeutic promise they may hold in areas including cancer treatment, glaucoma prevention and osteoporosis and bone mineralization promotion.…”

Alterations in the Plasma Proteome Induced by SARS-CoV-2 and MERS-CoV Reveal Biomarkers for Disease Outcomes for COVID-19 Patients

“…Complex proteomic data were generated between the sample groups as previously described. 16,22 The MS data were acquired in an m/z range of 50-2000 Da with a gradient acquisition run time of 120 min using ion-mobility separation experiments (HDMS E ). Each sample was analyzed in triplicate runs using the Mass Lynx platform (Version.…”

Immunomodulatory Mechanism and Potential Application of Dental Pulp-Derived Stem Cells in Immune-Mediated Diseases

“…They are usually obtained from the permanent teeth of adults [14], and also from the tissue of dead teeth or lesions (such as periodontitis, root resorption, pericoronitis, and osteopetrosis) [15][16][17]. Research has shown that dental pulp stem cells (DPSCs) in the inflamed dental pulp and DPSCs from inherited dental diseases were not damaged by the disease environment and had similar stem cell properties and immunosuppressive effects to healthy DPSCs [17][18][19]. DPSCs have MSCs properties and have the potential to differentiate into osteoblasts, adipocytes, and neuronal cells [20].…”