The Role of Collagen Crosslinking in Differentiation of Human Mesenchymal Stem Cells and MC3T3-E1 Cells

Abstract

Collagen is the main protein component of the extracellular matrix of bone, and it has structural and instructive properties. Collagen undergoes many post-translational modifications, including extensive crosslinking. Although defective crosslinking has been implicated in human syndromes (e.g., osteogenesis imperfecta or Ehlers-Danlos syndrome), it is not clear to what extent crosslinking is necessary for collagen's instructive properties during bone formation. Here we report that inhibition of collagen crosslinking in the mouse pre-osteoblast cell line MC3T3-E1 impairs the osteogenic program. Genome-wide expression profiling of beta-aminopropionitrile-treated and control cells revealed that matrix deposition by MC3T3-E1 cells provides a feed back signal, driving cells through the differentiation process, that is strongly impaired when crosslinking is inhibited. Inhibition of crosslinking did not affect osteogenic differentiation of human mesenchymal stem cells (hMSCs), shown by the expression of alkaline phosphatase and genome-wide gene expression analysis, although it enhances matrix mineralization. In conclusion, collagen crosslinking harbors instructive properties in MC3T3-E1 differentiation but plays a more-passive role in differentiation of bone marrow-derived hMSCs.

A Lox/CHOP‐10 crosstalk governs osteogenic and adipogenic cell fate by MSCs

“…Our findings reveal that Lox inhibition promotes BMP4‐induced osteogenesis, which contradicts previous reports about the functions of Lox in bone development 14, 42, 43, 44. Specifically, primary calvarial osteoblasts from Lox −/− mice exhibit decreased osteoblastic differentiation,14 and BAPN inhibits osteoblastic differentiation of MC3T3‐E1 preosteoblasts 44, 45. This discrepancy may be owing to the presence of BMP4, a molecule with both pro‐adipogenic and pro‐osteogenic effect, in that BAPN alone inhibited osteogenesis both in vitro (Figure S1) and in vivo (Figure S5), which was consistent with the previous study that Lox inhibit osteoblast differentiation.…”

A paradigm shift for bone quality in dentistry: A literature review

“…In addition, altered collagen cross-linking is frequently observed in aging and many systemic diseases [33,48,49] due to inappropriate post-translational modifications of collagen. It has been reported that impaired cross-linking in collagenous matrix affects osteoblast differentiation [70,71], indicating that collagen cross-linking also affects tissue turnover, which is another important determinant of bone quality. Therefore, the quantification and characterization of collagen cross-linking in bone may be useful for the diagnosis and understanding of bone status.…”

Uncultured Marrow Mononuclear Cells Delivered Within Fibrin Glue Hydrogels to Porous Scaffolds Enhance Bone Regeneration Within Critical-Sized Rat Cranial Defects

“…55,56 Similar effects have also been seen in collagen gels. 57 In the present study, we hypothesized that bone formation within a critical-sized defect would be enhanced using uncultured bmMNCs encapsulated in fibrin gels for delivery of the cells within model scaffolds made of poly(L-lactic acid) (PLLA) or coralline hydroxyapatite (HA). Scaffold properties were also expected to play a significant role on bone formation.…”