title: Diabetes-induced fibrotic matrix inhibits intramembranous bone healing.
abstract: Diabetes diminishes bone healing and ossification. Reduced bone formation in intramembranous ossification is known, yet the mechanism(s) behind impaired intramembranous bone healing are unclear. Here we report the formation of a fibrotic matrix during healing of intramembranous calvarial bone defects that appears to exclude new bone growth. Our histological analyses of 7-day and 14-day calvaria bone healing tissue in chemically-induced diabetic mice and non-diabetic mice showed the accumulation of a non-mineralized fibrotic matrix, likely as a consequence of unresolved hematomas under diabetic conditions. Elevated mRNA and enzyme activity levels of lysyl oxidase on day 7 in diabetic bone healing tissues also supports that the formation of a fibrotic matrix occurs in these tissues. Based on these findings, we propose that elevated fibroblast proliferation and formation of a non-mineralized fibrotic extracellular matrix in diabetes contributes to deficient intramembranous bone healing in diabetes. A greater understanding of this process has relevance to managing dental procedures in diabetics in which successful outcomes depend on intramembranous bone formation.
authors.affiliation: Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA, 02118, USA, Roozbeh.kh@gmail.com.
authors.forename: Roozbeh
authors.initials: R
authors.lastname: Khosravi
authors.forename: Philip C
authors.initials: PC
authors.lastname: Trackman