Osteopontin : its role during distraction osteogenesis healing
Date
2007
DOI
Authors
Al-Aql, Zainab S
Version
OA Version
Citation
Abstract
Introduction: Osteopontin (OPN) is a phosphoprotein found in the extracellular matrices of mineralized tissues and is believed to play a role in the remodeling of these matrices. OPN is also one of a limited number of genes that respond to mechanical strain. Distraction osteogenesis (DO) represents a unique in vivo surgical method of applied mechanical tension that induces new bone formation and therefore represents an ideal model to assess the multiple functional roles of osteopontin.
Materials and Methods: Tibia distraction osteogenesis was carried out using a monolateral fixator on male transgenic mice lacking osteopontin (OPN[-/-] C57B1/6) and their background strain (C57B1/6). MicroCT was used for quantitative assessment of DO regenerate size, microstructure and mineralization at the early and late consolidation phases. Histology and molecular analyses were used to evaluate cellular functions related to ECM formation, remodeling and bone resorption.
Results: In the absence of OPN, knock out mice displayed a reduced total volume of the bone regenerate at the early consolidation stage of tissue formation. However, as healing progressed this deficiency was corrected by the end of the period of consolidation. A comparison of the anabolic versus catabolic activities during distraction osteogenes is demonstrated that OPN[-/-] regenerate possessed larger numbers of osteoclasts per area of bone accompanied by an increased expression of their makers. Messenger RNAs encoding matrix metalloproteinases 2 and 9 that are associated with matrix remodeling were also induced by higher levels at the end of latency and early consolidation phases in the OPN deficient mice relative to the control animals. On the anabolic side OPN[-/-] mice displayed compensatory increase in the levels of collagen type 1 expression accompanied by an altered organization of its fibers whereas other ECM proteins displayed normal levels. Interesting, all three metalloproteinase inhibitors showed elevated expression over time and strain in the OPN[-/-] mice.
Conclusion: This study showed that OPN deficiency lead to structural alterations during the early periods of bone healing; however, during the later periods healing recovered and normal union was achieved. These studies suggest that the absence of OPN led to higher activity of both osteoclasts and osteoblasts demonstrating that insufficiencies in the expression of this extracellular matrix component effects both the anabolic and catabolic activities of coupled remodeling. Thus, the earlier increases in perhaps less than optimally functional osteoclasts are coupled with the subsequent elevation in osteoblastic activities.
Description
PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.
Thesis (D.Sc.D.)--Boston University, Goldman School of Dental Medicine, 2007 (Orthodontics).
Includes bibliography: leaves 96-103.
Thesis (D.Sc.D.)--Boston University, Goldman School of Dental Medicine, 2007 (Orthodontics).
Includes bibliography: leaves 96-103.
License
This work is protected by copyright. Downloading is restricted to the BU community. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.