Bone Abstracts

There have been considerable advances in our knowledge of how loss of androgens signalling leads to bone loss in aging male with hypogonadism. However, the roles of androgen actions on the skeletal growth remain limited. Recently, new insights into the function of and androgen receptor (AR), learned from human genetic mutations and gene targeting mouse models have contributed to emerged understanding of the androgenic effects on bone and cartilage in health and diseases. Here, we studied the roles of the androgen/AR signalling in regulating stem/progenitor cells by which the androgenic steroids act as anabolic hormones on promotion of bone growth. Lineage-tracing experiments revealed that osteochondroprogenitors expressing type II collage (Col2) gene encompasses early mesenchymal progenitor cells, which preferentially become chondrocytes. Inactivation of AR by cre recombinases driven by the Col2a1 promoter causes delayed endochondral bone formation, impaired chondrocyte proliferation and leading to a smaller skeleton in mice. Col2-ARKO male mice have shorter bone length compared to wild type mice. Mechanistically, AR promotes chondrogenic IGF-1 gene expression by demethylating H3-K27, thereby leading to promote proliferation of chondrogenic cells. AR silencing decreased proliferation of chondrogenic cells could be rescued by activation of IGF-1 signal. Together, these results establish AR as a key regulator of chondrogenesis and provide insights into the therapeutic potential of targeting AR in treating bone and cartilage-associated diseases.