Altered hematopoietic stem cell and osteoclast precursor frequency in cathepsin k null mice

Christian Jacome-Galarza, Do Yu Soung, Naga Suresh Adapala, Maureen Pickarski, Archana Sanjay, Le T. Duong, Joseph A. Lorenzo, Hicham Drissi

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1449-1457
Number of pages9
JournalJournal of Cellular Biochemistry
Volume115
Issue number8
DOIs
StatePublished - Aug 2014

Keywords

  • cathepsin K
  • hematopoiesis
  • osteoclast precursors
  • osteopetrosis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Altered hematopoietic stem cell and osteoclast precursor frequency in cathepsin k null mice'. Together they form a unique fingerprint.

Cite this