Cells Derived from Human Long Bone Appear More Differentiated and More Actively Stimulate Osteoclastogenesis Compared to Alveolar Bone-Derived Cells

Abstract

Osteoblasts derived from mouse skulls have increased osteoclastogenic potential compared to long bone osteoblasts when stimulated with 1,25(OH)2 vitamin D3 (vitD3). This indicates that bone cells from specific sites can react differently to biochemical signals, e.g., during inflammation or as emitted by bioactive bone tissue-engineering constructs. Given the high turn-over of alveolar bone, we hypothesized that human alveolar bone-derived osteoblasts have an increased osteogenic and osteoclastogenic potential compared to the osteoblasts derived from long bone. The osteogenic and osteoclastogenic capacity of alveolar bone cells and long bone cells were assessed in the presence and absence of osteotropic agent vitD3. Both cell types were studied in osteogenesis experiments, using an osteogenic medium, and in osteoclastogenesis experiments by co-culturing osteoblasts with peripheral blood mononuclear cells (PBMCs). Both osteogenic and osteoclastic markers were measured. At day 0, long bones seem to have a more late-osteoblastic/preosteocyte-like phenotype compared to the alveolar bone cells as shown by slower proliferation, the higher expression of the matrix molecule Osteopontin (OPN) and the osteocyte-enriched cytoskeletal component Actin alpha 1 (ACTA1). This phenotype was maintained during the osteogenesis assays, where long bone-derived cells still expressed more OPN and ACTA1. Under co-culture conditions with PBMCs, long bone cells also had a higher Tumor necrose factor-alfa (TNF-α) expression and induced the formation of osteoclasts more than alveolar bone cells. Correspondingly, the expression of osteoclast genes dendritic cell specific transmembrane protein (DC-STAMP) and Receptor activator of nuclear factor kappa-Β ligand (RankL) was higher in long bone co-cultures. Together, our results indicate that long bone-derived osteoblasts are more active in bone-remodeling processes, especially in osteoclastogenesis, than alveolar bone-derived cells. This indicates that tissue-engineering solutions need to be specifically designed for the site of application, such as defects in long bones vs. the regeneration of alveolar bone after severe periodontitis.

Although Anatomically Micrometers Apart: Human Periodontal Ligament Cells Are Slightly More Active in Bone Remodeling Than Alveolar Bone Derived Cells

“…Indeed, it was shown by Nomura et al (2012) and by Sanchez-Duffhues et al (2019) that PDL fibroblasts are an ideal source for making induced pluripotent stem cells. The morphology of alveolar bone derived cells in vitro is also in agreement with the study by Kelder et al (2020) , in which alveolar bone was compared to long bone cells. In that study, long bone cells presented a more cuboidal appearance, similar to the morphology of osteoblasts.…”

“…Likewise, PDL and alveolar bone cells hardly expressed late osteogenic marker DMP1, an important marker for bone mineralization. Low expression levels of DMP1 were also previously found ( Ruppeka-Rupeika et al, 2018 ; Kelder et al, 2020 ). This might indicate that under these circumstances, cells do not differentiate fully until the late osteoblast/osteocyte stage.…”

“…The authors extrapolated similarity in composition of the extracellular matrix between alveolar bone and other bone tissues to commonly shared osteogenic functions. Only recently we showed that alveolar bone cells and long bone cells may have a different morphology once cultured in vitro , indicating that cells from the two different types of bones may differ in their osteogenic and osteoclastogenic capacity ( Kelder et al, 2020 ).…”

3D bioprinting of tissue-specific osteoblasts and endothelial cells to model the human jawbone

“…summarised several studies concluding that there is indeed a physiological difference between osteogenic cells from jawbone versus long bones, making them mandatory for generation of a jawbone model 61 . In line with this, several jawbone models have been proposed based on the origin of the isolated osteoblasts 23 , 25 , 27 , 55 , 62 .…”

Molecular Mechanisms of Periodontal Disease

“…Thus, much scientific attention has been paid to the study of osteoblasts and osteoclasts. Kelder et al reported that osteoblastic cells isolated from long bone showed more significant osteogenic activity than those of alveolar bone [ 7 ]. As the novel molecular mechanisms underlying RANKL induction in osteoblasts, the significant role of LAMP-2, which is involved in the fusion of lysosomes with phagosomes, was discovered by Jansen et al [ 8 ].…”