Bone formation in rat calvaria ceases within a limited period regardless of completion of defect repair

Abstract

A bone defect that is not repaired with bone completely is designated a non-union defect or a critical-size defect. The biological mechanism that regulates the process of bone repair of the critical-size defect remains unknown. The present study was designed to investigate bone repair in a critical-size defect compared with that in a smaller or non-critical-size defect. Our original standardized rat calvarial bone defect model was used for the experiment. The rate of bone formation was examined with X-ray morphometry and the bone production of osteoblasts and osteocytes was assessed by molecular histology with in situ hybridization for type I collagen and osteocalcin. Formation of repaired bone ceased within 24 weeks in both critical- and non-critical-size defects i.e. regardless of completion of the defect repair. The results suggested that osteoblasts and osteocytes cease bone formation, and the differentiation of osteoblast progenitors declines in 24 weeks. Also, bone repair proceeds from the periosteum on both sides of the parietal bone but not from the surface of the bony edge around the original defect. The results could provide useful information for clinical research on bone repair.

Quantitative Analysis and Localization of mRNA Transcripts of Type I Collagen, Osteocalcin, MMP 2, MMP 8, and MMP 13 During Bone Healing in a Rat Calvarial Experimental Defect Model

“…Osteoblasts and osteocytes may cease degradation of ECM within a limited period, regardless of completion of the defect repair in the rat model, as we previously reported for production of ECM (Honma et al, 2008). Further investigation with this experimental model may help provide a greater understanding of the cellular and molecular events associated with the remodeling of the ECM during bone healing.…”

“…Our previous study using in situ hybridization demonstrated that osteoblasts and osteocytes no longer express bone matrix proteins in the repairing process of rat calvarial bone defects, and then bone healing ceases within a limited period, regardless of completion of the defect repair (Honma et al, 2008). However, how long osteoblasts and osteocytes keep producing bone matrix proteins, such as type I collagen and osteocalcin during the healing process, was not known.…”

“…Our previous study showed that the rate of bone matrix apposition per week during healing of the bone defect was highest in week 4 and decreased thereafter (Honma et al, 2008). A period of time that it takes for translation from mRNA to proteins and calcification of the bone matrix to be identified on radiographs may be involved in the differences in timing between the highest mRNA expression of the bone matrix proteins in week 2 and the highest rate of bone matrix apposition in week 4.…”

“…Extreme care was exercised to avoid injury to the midsagittal blood sinus and dura mater. The periosteum and skin flaps were returned and sutured (Honma et al, 2008).…”

“…calvarial bone defect (Honma et al, 2008). However, when and how these cells increase and decrease production of these proteins in the course of the healing process is not known.…”