The diverse origin of bone-forming osteoblasts

Abstract

Osteoblasts are the only cells that can give rise to bones in vertebrates. Thus, one of the most important functions of these metabolically active cells is mineralized matrix production. Because osteoblasts have a limited lifespan, they must be constantly replenished by preosteoblasts, their immediate precursors. Because disruption of the regulation of bone‐forming osteoblasts results in a variety of bone diseases, a better understanding of the origin of these cells by defining the mechanisms of bone development, remodeling, and regeneration is central to the development of novel therapeutic approaches. In recent years, substantial new insights into the origin of osteoblasts—largely owing to rapid technological advances in murine lineage‐tracing approaches and other single‐cell technologies—have been obtained. Collectively, these findings indicate that osteoblasts involved in bone formation under various physiological, pathological, and therapeutic conditions can be obtained from numerous sources. The origins of osteoblasts include, but are not limited to, chondrocytes in the growth plate, stromal cells in the bone marrow, quiescent bone‐lining cells on the bone surface, and specialized fibroblasts in the craniofacial structures, such as sutures and periodontal ligaments. Because osteoblasts can be generated from local cellular sources, bones can flexibly respond to regenerative and anabolic cues. However, whether osteoblasts derived from different cellular sources have distinct functions remains to be investigated. Currently, we are at the initial stage to aptly unravel the incredible diversity of the origins of bone‐forming osteoblasts. © 2021 American Society for Bone and Mineral Research (ASBMR).

Neuronal Induction of Bone‐Fat Imbalance through Osteocyte Neuropeptide Y

“…[ 9,11,25,40 ] Nevertheless, Dmp1‐Cre can inevitably target a minority of osteoblasts that express DMP1. Mature osteoblasts and bone lining cells (derived from mature osteoblasts and located on the BS) [ 41 ] will also be targeted by Dmp1‐Cre due to their DMP1 expression. In our study, we did not find and use a perfect Cre model that only targets osteocytes.…”

Site-Specific Fracture Healing: Comparison between Diaphysis and Metaphysis in the Mouse Long Bone

“…Periosteal cells appear to be the major source of progenitors for cartilaginous callus [27,37]. Other cells from different sources may also contribute to callus formation, including the bone marrow [38], vessel walls [39], surrounding muscles [40], and circulation [41]. SSCs within the periosteum show the higher regenerative potential than those in the bone marrow [42].…”

Pathological differences in the bone healing processes between tooth extraction socket and femoral fracture

“…Recent advances in cell lineage-tracing techniques provide a great opportunity to understand the lineages and fates of cells participating in skeletal tissue formation and regeneration ( Debnath et al, 2018 ; Matsushita et al, 2020 ; Mizoguchi and Ono, 2021 ; Mizoguchi et al, 2014 ; Ransom et al, 2016 ; Shi et al, 2017 ). For example, Debnath et al (2018) discovered that periosteal stem cells located in long bones and calvaria in mice could form bone by intramembranous ossification, whereas they acquired the capacity to undergo endochondral ossification depending on their plasticity.…”