Cxcl9l and Cxcr3.2 regulate recruitment of osteoclast progenitors to bone matrix in a medaka osteoporosis model
Quang Tien Phan, Wen Hui Tan, Ranran Liu, Sudha Sundaram, Anita Buettner, Susanne Kneitz, Benedict Cheong, Himanshu Vyas, Sinnakaruppan Mathavan, Manfred Schartl, Christoph Winkler
Abstract
Significance Bone remodeling requires a balanced interplay of osteoblasts and osteoclasts. While the intercellular signaling that triggers bone cell differentiation is well understood, it remains unclear how bone progenitor cells are recruited to remodeling sites. Various chemokines are upregulated under osteoporotic conditions. However, whether they are involved in progenitor recruitment or instead have inflammatory roles is unknown. Here we used a medaka fish osteoporosis model to identify the chemokine ligand Cxcl9l and receptor Cxcr3.2 as essential to control osteoclast progenitor recruitment and differentiation at bone resorption sites. Cxcr3.2 activity can be blocked by small-molecule inhibitors that protect bone from osteoporotic insult. Our study demonstrates the potential of fish for osteoporosis drug discovery and opens avenues for future osteoporosis therapy.