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

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.

AFGHAN MUTATION OF CA-II GENE

Carbonic anhydrase-II deficiency is an autosomal recessive disorder groundedon a triad of cerebral calcification, osteopetrosis and renal tubular acidosis away in whichproximal tubules, distal collecting ducts or combined.1 Other features include growth andmental retardation along with the complications of osteopetrosis.2 The only treatment to curethe calcification is allogeneic bone marrow stem cell replacement; however it does not have anyconsiderable effect on the renal lesions3 We report a case of a 3 week old male child of Afghanorigin with all these features who was clinically diagnosed as having carbonic anhydrase type IIdeficiency however unfortunately the baby passed during cranioplasty and genetic testing forenzyme deficiency could not be done. Our aim to present this case of a male child of Afghanorigin is to enhance the awareness about this rare syndrome in our medical community andinviting further research for a possible Afghan mutation of CA-II gene.