Osteopetrosis (literally “stone bone”) is a clinically and genetically diverse rare bone disease showing increased bone density on radiographs. Osteopetrosis results from abnormalities in either differentiation or function of the bone cells. The most severe form, Autosomal Recessive Osteopetrosis (ARO) affects children in their early life and leads to death if not adequately treated. ARO is characterized by dense but fragile bones, narrower bone marrow cavity leading to a reduced number of blood cells and an enlargement of liver and spleen; cranial nerve compression, blindness and/or deafness; and a few additional multi-systemic changes.

Osteopetrosis can result from defects in the function of the bone resorbing cells (osteoclasts, more common) or bone forming cells (osteoblasts). Understanding the pathomolecular mechanism of these conditions is of utmost important for the diagnosis and future treatment of the patients.

In our lab, we are currently studying a model of osteoblast-driven osteopetrosis which results from an overexpression of Trib1 under the col2a1 promoter.

Xray images of animals overexpressing Trib 1 (right panel), showing clear hallmarks of osteopetrosis – denser bones, hip dysplasia,no incisors or maxillary molars with mandibular molars un-erupted and hypoplastic (unpublished data, Pirog lab).

Histology images of 6 week old knee joints (H&E staining) showing narrower bone marrow spaces in the Trib1 mutant animals (unpublished data, Pirog lab).