ID1 is a key regulator for bone and bone marrow hematopoietic niche homeostasis.

摘要

Although bone remodeling and hematopoiesis are anatomically juxtaposed, little is known about the genetic regulation shared by these two processes. Here, we report a new role for the inhibitor of differentiation 1 (Id1) gene in bone remodeling and maintenance of the bone marrow hematopoietic niche. Id1-/- mice exhibited osteoporosis, characterized by reduced bone mass and increased bone fragility. We found that loss of Id1 increased osteoclast differentiation, both in vivo and in vitro, suggesting a cell autonomous role for Id1 as a negative regulator of osteoclast differentiation. Even though hematopoietic stem cell (HSC) proliferation was increased in vivo in Id1-/- mice, Id1-/- HSCs had the same proliferation potential as wild-type HSCs when cultured in vitro, indicating that cell extrinsic signals were responsible for the enhanced cycling of Id1-/- HSCs in vivo. Accordingly, key osteoclast-derived stromal regulatory factors, such as cathepsin K, were increased in the HSC niche of Id1-/- mice. Lastly, we were able to demonstrate a mechanism for transcriptional control of osteoclast-associated genes by Id1. In summary, we have identified a dynamic cross-talk between the bone and bone marrow HSC niche. This discovery will further guide our understanding of the delicate balance of Id1 gene expression in normal physiological and pathological events, such as aging, osteoporosis, and malignancy.