Bone is a complex tissue, predominately comprised of collagen and hydroxyapatite mineral. Bone cells, osteoblasts and osteocytes (responsible for bone formation), and osteoclast (responsible for bone resorption) regulate the bone material content. Cell surface receptors, such as discoidin domain receptor 1 (DDR1) present on bone cells can serve as biomarkers of aberrant bone remodeling. DDR1 is a receptor tyrosine kinase which binds to collagen as its ligand. Previous studies from our lab and others have shown that DDR1 regulates bone remodeling in both development and in aging by altering osteoblast or osteoclast population. In this study, we investigated how DDR1 affects bone material properties at the macro and microscale level. Long bones (femurs) extracted from 6- and 12-month old DDR1 knockout (KO) and wild-type (WT) mice were subjected to three point bending and nanoindentation. Bone mineral content was evaluated using micro-CT and thermogravimetric analysis. Collagen fibers and fibril structure were assessed using picrosirius red and transmission electron microscopy. Our results show that the mechanical properties of DDR1 KO bones were differentially regulated with age as compared to their WT counterparts. Significant differences were noted in the collagen and osteocyte environment but not in the mineral content. Our results signify how collagen receptors like DDR1 in bone cells can impact the bone matrix environment with aging. This can be especially relevant for age-related bone diseases such as osteoporosis.
Gunjan Agarwal (2026) studied this question.