Early reversal cells in adult human bone remodeling: osteoblastic nature, catabolic functions and interactions with osteoclasts

Abstract

The mechanism coupling bone resorption and formation is a burning question that remains incompletely answered through the current investigations on osteoclasts and osteoblasts. An attractive hypothesis is that the reversal cells are likely mediators of this coupling. Their nature is a big matter of debate. The present study performed on human cancellous bone is the first one combining in situ hybridization and immunohistochemistry to demonstrate their osteoblastic nature. It shows that the Runx2 and CD56 immunoreactive reversal cells appear to take up TRAcP released by neighboring osteoclasts. Earlier preclinical studies indicate that reversal cells degrade the organic matrix left behind by the osteoclasts and that this degradation is crucial for the initiation of the subsequent bone formation. To our knowledge, this study is the first addressing these catabolic activities in adult human bone through electron microscopy and analysis of molecular markers. Periosteoclastic reversal cells show direct contacts with the osteoclasts and with the demineralized resorption debris. These early reversal cells show (1) ¾-collagen fragments typically generated by extracellular collagenases of the MMP family, (2) MMP-13 (collagenase-3) and (3) the endocytic collagen receptor uPARAP/Endo180. The prevalence of these markers was lower in the later reversal cells, which are located near the osteoid surfaces and morphologically resemble mature bone-forming osteoblasts. In conclusion, this study demonstrates that reversal cells colonizing bone surfaces right after resorption are osteoblast-lineage cells, and extends to adult human bone remodeling their role in rendering eroded surfaces osteogenic.

Coupling of Bone Resorption and Formation in Real Time: New Knowledge Gained From Human Haversian BMUs

“…A ), as typically shown in the literature through conventional histological staining . As expected, mononucleated cells positive for osteoblast lineage cell markers (but not for TRAcP or CatK) colonize the newly generated walls of the tunnel as soon as the osteoclast‐front moves away (Fig. F, G, I, J, L, M ).…”

“…The relevance of the present observations to cancellous bone is also supported by basic observations, such as the frequent presence of reversal/osteoprogenitor cells incidentally shown at both sides of osteoclasts on eroded surfaces, thereby indicating an interruption of the reversal phase by resorption episodes. Intimate interactions between osteoclasts and reversal cells were also reported in cancellous bone . Finally, initiation of bone formation in cancellous bone also appears to require a critical cell density, as mentioned above …”

Inhibition of cathepsin K promotes osseointegration of titanium implants in ovariectomised rats

“…Osteoclastic bone resorption and osteoblast-mediated bone formation are coupled in the mature skeleton36. Following OVX surgery in this study, osteoporotic rodent models were successfully established, and the expressions of osteoclastic genes increased.…”

Osteoclast differentiation from human blood precursors on biomimetic calcium-phosphate substrates

“…This method closely mimics the bidirectional osteoclast/osteoblast interaction occurring in vivo at the sites of bone remodeling [14].…”