Altered Hematopoietic Stem Cell and Osteoclast Precursor Frequency in Cathepsin K Null Mice

• Published in: Journal of cellular biochemistry Vol. 115; no. 8; pp. 1449 - 1457
• Main Authors: Jacome-Galarza, Christian, Soung, Do Yu, Adapala, Naga Suresh, Pickarski, Maureen, Sanjay, Archana, Duong, Le T., Lorenzo, Joseph A., Drissi, Hicham
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.08.2014; Wiley Subscription Services, Inc
• Subjects: Animals; Bone Resorption - genetics; Bone Resorption - pathology; CATHEPSIN K; Cathepsin K - genetics; Cathepsin K - metabolism; Fracture Healing - genetics; HEMATOPOIESIS; Hematopoietic Stem Cells - metabolism; Hematopoietic Stem Cells - pathology; Mice; Mice, Knockout; OSTEOCLAST PRECURSORS; Osteoclasts - metabolism; Osteoclasts - pathology; Osteogenesis; OSTEOPETROSIS; Osteopetrosis - genetics; Osteopetrosis - pathology; CATHEPSIN K; HEMATOPOIESIS; OSTEOPETROSIS; OSTEOCLAST PRECURSORS
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.24801

ABSTRACT Cathepsin K (CatK) is a lysosomal cysteine protease necessary for bone resorption by osteoclasts (OCs), which originate from myeloid hematopoietic precursors. CatK‐deficient (CatK−/−) mice show osteopetrosis due to defective resorption by OCs, which are increased in number in these mice. We investigated whether genetic ablation of CatK altered the number of hematopoietic stem cells (HSCs) and OC precursor cells (OCPs) using two mouse models: CatK−/− mice and a knock‐in mouse model in which the CatK gene (ctsk) is replaced by cre recombinase. We found that CatK deletion in mice significantly increased the number of HSCs in the spleen and decreased their number in bone marrow. In contrast, the number of early OCPs was unchanged in the bone marrow. However, the number of committed CD11b+ OCPs was increased in the bone marrow of CatK−/− compared to wild‐type (WT) mice. In addition, the percentage but not the number of OCPs was decreased in the spleen of CatK−/− mice relative to WT. To understand whether increased commitment to OC lineage in CatK−/− mice is influenced by the bone marrow microenvironment, CatKCre/+ or CatKCre/Cre red fluorescently labeled OCPs were injected into WT mice, which were also subjected to a mid‐diaphyseal femoral fracture. The number of OCs derived from the intravenously injected CatKCre/Cre OCPs was lower in the fracture callus compared to mice injected with CatK+/Cre OCPs. Hence, in addition to its other effects, the absence of CatK in OCP limits their ability to engraft in a repairing fracture callus compared to WT OCP. J. Cell. Biochem. 115: 1449–1457, 2014. © 2014 Wiley Periodicals, Inc.