UC San Diego

Throughout one’s life a person’s bone constantly goes through bone resorption and bone formation in a process called bone remodelling. Bone diseases such as osteoporosis are caused by a dysregulation of this bone remodelling. Bone resorption is well understood, but the molecular mechanism and biology of bone formation is not fully understood. It is known that osteoblasts (bone forming cells) form a 5-10 um layer of osteoid (bone matrix) and calcify (mineralize) it to form bone. However, the exact process by which osteoblasts calcify osteoid is not fully understood. In this study we show that it is possible for lamellar bone formation to occur via a two step “seed-grow” mechanism. In this mechanism osteoblasts first seed osteoid with many small mineral crystals, after which the seed crystals go on to grow and calcify osteoid to form the final bone tissue. The seed crystals grow by taking calcium and phosphate from the circulating blood that bathes osteoid and therefore do not require osteoblasts for mineral growth past the initial seeding step. The seed-grow mechanism was tested via a trabecular bone block model system, where blocks of bovine trabecular bone were decalcified (demineralized) to recreate the initial osteoid material (bone collagen blocks). Bone collagen blocks were then artificially seeded with many small crystals via a previously developed technique and incubated in adult bovine serum without osteoblasts. The bone collagen blocks recalcified (remineralized) and hardened, eventually forming a complete, freestanding mineral continuum – a characteristic of the mineral phase in normal bone.