Cathepsin K is required for maintenance and regeneration of lymphopoiesis in vivo

Cathepsin K (CTSK) is a major collagen-degrading protease in osteoclasts. Defects in CTSK activity are directly linked to skeletal abnormalities such as osteoporosis and osteopetrosis. The role of CTSK in cell types other than osteoclasts is poorly understood. Stromal cells, which maintain hematopoietic stem cells (HSCs) during culture, show high transcription of the gene. Here, we investigated the influence of the absence of on the hematopoietic system. We found that cultures with Lineage SCA1 KIT (LSK) cells on deficient stromal cells display reduced colony formation and proliferation, with increased differentiation, whilst subsequent experiments show impaired HSC maintenance of lymphopoiesis of cultured cells. , deletion of does not show gross effects on early hematopoiesis or myelopoiesis. But, in the bone marrow (BM), T cell numbers are significantly reduced. Lymphocyte deregulation is also found in transplantation experiments, which revealed that is required for optimal regeneration not only of T cells, but also of B cells. Interestingly, environmental is involved in both B- and T-lymphopoiesis, but T cell development in the bone marrow additionally requires an intrinsic -dependent process. Thus, our study shows that is required for the maintenance of HSCs and proper lymphopoiesis and .