Osteoblast Recruitment Routes in Human Cancellous Bone Remodeling

Abstract

It is commonly proposed that bone forming osteoblasts recruited during bone remodeling originate from bone marrow perivascular cells, bone remodeling compartment canopy cells, or bone lining cells. However, an assessment of osteoblast recruitment during adult human cancellous bone remodeling is lacking. We addressed this question by quantifying cell densities, cell proliferation, osteoblast differentiation markers, and capillaries in human iliac crest biopsy specimens. We found that recruitment occurs on both reversal and bone-forming surfaces, as shown by the cell density and osterix levels on these respective surfaces, and that bone formation occurs only above a given cell density. Canopies appeared an important source of osteoprogenitors, because (i) canopy cells proved to be more proliferative and less differentiated than bone surface cells, as shown by the inverse levels of Ki-67 and procollagen-3 N-terminal peptide versus osterix, and (ii) canopy cell densities, found to decline with age, and canopy-capillary contacts above eroded surfaces correlated positively with osteoblast density on bone-forming surfaces. Furthermore, we showed that bone remodeling compartment canopies arise from a mesenchymal envelope surrounding the red bone marrow, which is lifted and hypertrophied on initiation of bone resorption. This study, together with earlier reports, led to a model in which canopies and nearby capillaries are critical for reaching the osteoblast density required for bone formation.

A reversal phase arrest uncoupling the bone formation and resorption contributes to the bone loss in glucocorticoid treated ovariectomised aged sheep

“…The collective characteristics of the arrested and active Rv.S are in line with the notion that the initiation of the bone formation demands that a critical number of osteoblastic progenitors, i.e. reversal cells, are recruited and matured during the reversal phase [14,20,44]. According to this notion, the insufficient recruitment and maturation of the osteoblastic progenitors on the arrested Rv.S inhibits the transformation from the reversal phase to the bone formation phase.…”

“…According to this notion, the insufficient recruitment and maturation of the osteoblastic progenitors on the arrested Rv.S inhibits the transformation from the reversal phase to the bone formation phase. Here the insufficient recruitment of osteoblastic progenitors to the arrested Rv.S in the GC-treated OVX sheep may be facilitated by the absence of canopies above the arrested Rv.S, since canopies have been reported to play a key role in the recruitment of osteoblastic progenitors to the bone surface during the reversal phase [14,23,44]. Collectively, the reported uncoupling of the bone formation and resorption during the reversal phase in the GC-treated OVX sheep strongly resembles the uncoupled remodelling process reported in patients with GC-induced osteoporosis [23,24].…”

“…The bone remodelling process is conducted by numerous microscopic units, which includes three tightly coordinated sequential events: bone resorption by osteoclasts (OCs), an intermediate reversal phase and bone formation by osteoblasts (OBs) [13,14]. The cancellous bone remodelling process is separated from the marrow cavity by a canopy of flattened osteoblastic cells, forming an enclosed bone remodelling compartment (BRC) [15,16].…”

Assessment of bone vascularization and its role in bone remodeling

“…11,13 Recently, Adams' team published outstanding low magnification images of immunofluorescence-labeled vessels on 300-mm-thick frozen decalcified mouse whole tibia sections. 45 Finally, it is also possible to perform in vivo vessel labeling by intravascular injection of antibodies 46 or isolectin, 37 followed by in vivo or ex vivo confocal/ multiphoton microscopy.…”

“…Bone vessels bring osteoclast precursors at the bone surface where remodeling is about to take place and 'feed' the remodeling unit with new cells as long as necessary ( Figure 1). As for the osteoblastic lineage, studies suggest that osteoprogenitors could be recruited from circulating cells, 7 differentiated from pericytes, 8,9 or from cells located in the canopy 10 that isolate the bone remodeling compartment from the bone marrow 11,12 (Figure 1; top). Interestingly, canopy cells are in close contact with capillaries and Delaissé 's team recently demonstrated that vessel positioning relative to the bone surface was highly dependent on the remodeling status of the bone remodeling compartment, 13 suggesting substantial vessel plasticity.…”