Bone Microarchitecture Is Dependent Upon Collagen α1(XI) Expression During Development

Collagen type XI is an essential component of the collagen fibrils within the developing skeleton. It is a quantitatively minor member of the fibrillar collagens that plays a regulatory role in the assembly of embryonic collagen fibrils as the diameter of collagen fibrils is dependent on the presence of Collagen α1(XI). However, very little is known about the role of collagen type XI in bone microarchitecture formation. In this study, skeletal mineralization was evaluated in the absence and presence of Collagen α1(XI) comparing the chondrodysplasia (cho) mouse embryo to wildtype. The data presented support a role for collagen type α1(XI) in skeletal development that is distinct from its function in nucleating the formation and limiting the diameter of cartilage type II collagen fibrils. Established characteristics of the cho mouse were apparent in the mouse included in this study, including a shortened snout, and short, wide long-bones with flared metaphyses. The cho mouse humerus was 55% the length of the wildtype humerus and approximately 35% wider at the diaphysis and metaphyses. Quantification of the differences in the humerus, vertebral column, and ribcage of the cho and wildtype mice was carried out using high-resolution three-dimensional models that were created from x-ray microcomputed tomography images. Analysis revealed differences in bone density, size and microarchitecture. The differences in skeletal properties between these mice were analyzed by determining bone mineral density (BMD) calculations and three-dimensional measures of microarchitecture (BV/TV, Tb.Th, Tb.N, Tb.Sp). Results indicated that bone mineral density was increased in the absence of collagen α1(XI) in humerus, vertebrae, and the anterior rib samples of the cho mouse. The increase in bone density correlated with an observed increase in trabecular number, trabecular thickness, and percent bone volume, as well as a decrease in trabecular separation in the humerus, ribs, and vertebrae. In contrast, cortical bone mineral density was similar in wildtype and cho mice. A function for Collagen α1(XI) in the establishment of bone microarchitecture during embryonic development is supported by this data. Future studies will focus on Collagen α1(XI) in bone formation and mineralization by osteoblasts, and new functions for Collagen α1(XI) in non-cartilaginous tissues of the skeleton.