The role of the extracellular matrix protein SPOCK2 for bone physiology and hematopoiesis

Abstract

The bone marrow microenvironment (BMM) consists of different cellular and acellular components. These components synergize in regulating the process of hematopoiesis. Various extracellular matrix proteins are found amongst the acellular components. Secreted protein acidic and rich in cysteine (SPARC) is amongst the most abundant glycoproteins in bone. Sparc/osteonectin, cwcv, and Kazal-like domains proteoglycan 2 (SPOCK2) is a member of the SPARC family, and its role in bone metabolism and hematopoiesis has not been investigated. Using female mice deficient for SPOCK2, we assessed the role of SPOCK2 in influencing bone formation, the BMM and hematopoiesis. Using micro-computed tomography we found a significant decrease in trabecular bone volume, bone mineral density and thickness, but increased cortical mineral density in SPOCK2 knockout (KO) versus wildtype (WT) bones. C-terminal telopeptide of type I collagen, a measure of bone resorption, was significantly increased in bone marrow supernatants of SPOCK2 KO mice. In the hematopoietic compartment we found an increase in hematopoietic stem cells, but a decrease of mesenchymal stromal cells and adipocytes in the bone marrow of SPOCK2 KO mice compared to control mice. Megakaryocytes were increased in SPOCK2 KO mice. In summary, deficiency of SPOCK2 leads to several alterations in the BMM. The hematopoietic effects may be due to hematopoietic cell-intrinsic effects in SPOCK2-deficient cells or due to a SPOCK2-deficient niche or both.