Hurler disease bone marrow stromal cells exhibit altered ability to support osteoclast formation

Mucopolysaccharidosis type I (MPS IH; Hurler syndrome) is a rare genetic disorder, caused by mutations in the IDUA gene, resulting in the deficiency of α-L-iduronidase enzyme activity and intra-cellular accumulation of glycosaminoglycans. A characteristic skeletal phenotype is one of the many clinical manifestations in Hurler disease. As the mechanism(s) underlying these skeletal defects are not completely understood, and bone and cartilage are mesenchymal lineages, we focused on the characterization of mesenchymal cells isolated from bone marrow (BM) of Hurler patients. IDUA mutated BM stromal cells (BMSC) derived from MPS I patients, exhibited decreased IDUA activity, consistent with the disease genotype. The expansion rate, phenotype, telomerase activity, and differentiation capacity towards adipocytes, osteoblasts, chondrocytes and smooth muscle cells in vitro of 3 MPS I BMSC lines were similar to that of BMSC from age matched normal control donors. MPS I BMSC had also similar in vivo osteogenic capacity as normal BMSC. However, MPS I BMSC displayed increased capacity to support osteoclastogenesis which may correlate with the upregulation of the RANKL/RANK/OPG molecular pathway in MPS I BMSC compared to normal BMSC.