MedicalResearch.com Interview with: Ricardo Battaglino, Ph.D. Department of Mineralized Tissue Biology The Forsyth Institute, Cambridge, Massachusetts Department of Oral Medicine, Infection, and Immunity Harvard School of Dental Medicine, Boston, Massachusetts Medical Research: What is the background for this study? What are the main findings? Dr. Battaglino: Mutations in sorting nexin 10 (Snx10) have recently been found to account for roughly 4% of all human malignant osteopetrosis, some of them fatal. To study the disease pathogenesis, we investigated the expression of Snx10 and created mouse models in which Snx10 was knocked down globally or knocked out in osteoclasts. We found that Snx10, a molecule expressed in osteoclasts, was also expressed in the stomach. Studies in tissue specific or global knock-down mice showed that Snx10 deficiency resulted in a phenotype that was a consequence of deficiencies in both osteoclasts and gastric zymogenic cells. Our studies add to a growing list of genes, including atp6i (Tcirg1), whose expression is required both in bone and stomach to maintain normal gastric acidification and calcium absorption. Medical Research: What should clinicians and patients take away from your report? Dr. Battaglino: Our work provides additional insight into the mechanisms governing the regulation of bone accrual by the gastrointestinal tract. Because osteopetrorickets has not been described clinically in Snx10-related osteopetrosis, these findings highlight the importance of considering impaired acidification in both stomach and bone in osteopetrotic patients with mutations in SNX10 and other genes with similar patterns of expression and activities. Reliance solely on hematopoietic stem cell transplantation can leave hypocalcemia uncorrected with sometimes fatal consequences. Because defects in gastric differentiation and/or gastric acidification may cause or contribute to hypocalcemia, bone insufficiency, and early death, our results suggest that dietary calcium supplementation could be a life-saving intervention in these patients. (more…)