Csf1 from marrow adipogenic precursors is required for osteoclast formation and hematopoiesis in bone

Abstract

Colony-stimulating factor 1 (Csf1) is an essential growth factor for osteoclast progenitors and an important regulator for bone resorption. It remains elusive which mesenchymal cells synthesize <i>Csf1</i> to stimulate osteoclastogenesis. We recently identified a novel mesenchymal cell population, marrow adipogenic lineage precursors (MALPs), in bone. Compared to other mesenchymal subpopulations, MALPs expressed <i>Csf1</i> at a much higher level and this expression was further increased during aging. To investigate its role, we constructed MALP-deficient <i>Csf1</i> CKO mice using <i>Adipoq^Cre</i>. These mice had increased femoral trabecular bone mass, but their cortical bone appeared normal. In comparison, depletion of Csf1 in the entire mesenchymal lineage using <i>Prrx1^Cre</i> led to a more striking high bone mass phenotype, suggesting that additional mesenchymal subpopulations secrete Csf1. TRAP staining revealed diminished osteoclasts in the femoral secondary spongiosa region of <i>Csf1</i> CKO<i>^Adipoq</i> mice, but not at the chondral-osseous junction nor at the endosteal surface of cortical bone. Moreover, <i>Csf1</i> CKO<i>^Adipoq</i> mice were resistant to LPS-induced calvarial osteolysis. Bone marrow cellularity, hematopoietic progenitors, and macrophages were also reduced in these mice. Taken together, our studies demonstrate that MALPs synthesize Csf1 to control bone remodeling and hematopoiesis.