Quiescent Bone Lining Cells Are a Major Source of Osteoblasts During Adulthood

Abstract

The in vivo origin of bone-producing osteoblasts is not fully defined. Skeletal stem cells, a population of mesenchymal stem cells resident in the bone marrow compartment, are thought to act as osteoprogenitors during growth and adulthood. Quiescent bone lining cells (BLCs) have been suggested as a population capable of activation into mature osteoblasts. These cells were defined by location and their morphology and studies addressing their significance have been hampered by their inaccessibility, and lack of markers that would allow for their identification and tracing. Using lineage tracing models, we have observed labeled osteoblasts at time points extending beyond the reported lifespan for this cell type, suggesting continuous reactivation of BLCs. BLCs also make a major contribution to bone formation after osteoblast ablation, which includes the ability to proliferate. In contrast, mesenchymal progenitors labeled by Gremlin1 or alpha smooth muscle actin do not contribute to bone formation in this setting. BLC activation is inhibited by glucocorticoids, which represent a well-established cause of osteoporosis. BLCs express cell surface markers characteristic of mesenchymal stem/progenitors that are largely absent in osteoblasts including Sca1 and Leptin Receptor. BLCs also show different gene expression profiles to osteoblasts, including elevated expression of Mmp13, and osteoclast regulators RANKL and macrophage colony stimulating factor, and retain osteogenic potential upon transplantation. Our findings provide evidence that bone lining cells represent a major source of osteoblasts during adulthood.

Amplifying Bone Marrow Progenitors Expressing α‐Smooth Muscle Actin Produce Zonal Insertion Sites During Tendon‐to‐Bone Repair

“…In addition, it labels quiescent adult progenitors within periosteum, epitenon, skeletal muscle, and dental pulp that activate in response to injury. Unlike growing bone, fewer quiescent mesenchymal progenitors within the adult bone marrow express αSMA compared with the periosteum, therefore there is minimal contribution of these cells to intramembranous bone formation within the medullary cavity following injury . We found similar results following ACL reconstruction in this study where the contribution of SMA‐labeled cells was rather low (Fig.…”

Basis of bone metabolism around dental implants during osseointegration and peri‐implant bone loss

“…Moreover, BLCs exert a prominent function during bone resorption demonstrated by their ability to express key ostoclastogenesis markers including macrophage colony‐stimulating factor receptor and receptor activator of nuclear factor kappa‐B ligand (RANKL) . BLCs have been shown to be in close contact with osteoclasts and may also modulate bone remodeling .…”

Extracellular matrix networks in bone remodeling

“…While the ECM of the bone-lining cells is not well-described, these cells are proposed to serve a regulatory role and may be a significant source of mature osteoblasts in adults (Matic and Kalajzic, 2014). These OsteoMac cells are reported to play a regulatory role in bone formation and resorption, and during these processes, can form a remodeling 'canopy'.…”