Gene Expression Dynamics During Bone Healing and Osseointegration

Division of Periodontology, Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA.
Journal of Periodontology (Impact Factor: 2.71). 12/2010; 82(7):1007-17. DOI: 10.1902/jop.2010.100577
Source: PubMed


Understanding the molecular features of bone repair and osseointegration may aid in the development of therapeutics to improve implant outcomes. The purpose of this investigation is to determine the gene expression dynamics during alveolar bone repair and implant osseointegration.
An implant osseointegration preclinical animal model was used whereby maxillary defects were created at the time of oral implant placement, while a tooth extraction socket healing model was established on the contralateral side of each animal. The surrounding tissues in the zone of the healing defects were harvested during regeneration for temporal evaluation using histology, immunohistochemistry, laser capture microdissection, and quantitative reverse transcription-polymerase chain reaction for the identification of a panel of 17 putative genes associated with wound repair.
In both models, three distinct expression patterns were displayed: 1) genes that are slowly increased during the healing process, such as bone morphogenetic protein 4, runt-related transcription factor 2, and osteocalcin; 2) genes that are upregulated at the early stage of healing and then downregulated at later stages, such as interleukin and chemokine (C-X-C motif) ligands 2 and 5; and 3) genes that are constitutively expressed over time, such as scleraxis. Although some similarities between osseointegration and tooth extraction socket were seen, distinct features developed and triggered a characteristic coordinated expression and orchestration of transcription factors, growth factors, extracellular matrix molecules, and chemokines.
Characterization of these events contributes to a better understanding of cooperative molecular dynamics in alveolar bone healing, and highlights potential pathways that could be further explored for the enhancement of osseous regenerative strategies.

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Available from: Qiming Jin, Dec 23, 2013
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    • "Similar studies have been conducted in dogs [39], but mice offer a wide array of molecular and cellular tools with which to analyze the cellular and tissue-level responses that are unavailable for canine species. Other groups [19] [20] [21] have used rodents with similar maxillary models, where implant is placed in a ridge defect model where a tooth never existed. Collectively, these studies and ours show that oral implant osseointegration is achievable in a rodent model. "
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    ABSTRACT: Many of our assumptions concerning oral implant osseointegration are extrapolated from experimental models studying skeletal tissue repair in long bones. This disconnect between clinical practice and experimental research hampers our understanding of bone formation around oral implants and how this process can be improved. We postulated that oral implant osseointegration would be fundamentally equivalent to implant osseointegration elsewhere in the body. Mice underwent implant placement in the edentulous ridge anterior to the first molar and peri-implant tissues were evaluated at various timepoints after surgery. Our hypothesis was disproven; oral implant osseointegration is substantially different from osseointegration in long bones. For example, in the maxilla peri-implant pre-osteoblasts are derived from cranial neural crest whereas in the tibia peri-implant osteoblasts are derived from mesoderm. In the maxilla, new osteoid arises from periostea of the maxillary bone but in the tibia the new osteoid arises from the marrow space. Cellular and molecular analyses indicate that osteoblast activity and mineralization proceeds from the surfaces of the native bone and osteoclastic activity is responsible for extensive remodeling of the new peri-implant bone. In addition to histologic features of implant osseointegration, molecular and cellular assays conducted in a murine model provide new insights into the sequelae of implant placement and the process by which bone is generated around implants.
    Full-text · Article · Jul 2013 · Bone
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    • "The two healing models developed distinct features and triggered a characteristic coordinated expression and orchestration of transcription factors, growth factors, extracellular matrix molecules, and chemokines. These groundbreaking findings open new horizons to researchers, which might lead to a better understanding of the cooperative molecular dynamics in alveolar bone healing [105]. "
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    ABSTRACT: Following tooth extraction, the alveolar ridge undergoes an inevitable remodeling process that influences implant therapy of the edentulous area. Socket grafting is a commonly adopted therapy for the preservation of alveolar bone structures in combination or not with immediate implant placement although the biological bases lying behind this treatment modality are not fully understood and often misinterpreted. This review is intended to clarify the literature support to socket grafting in order to provide practitioners with valid tools to make a conscious decision of when and why to recommend this therapy.
    Full-text · Article · Jun 2012 · International Journal of Dentistry
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    • "But, a number of biologic mechanisms is involved in the osseointegration complex process, some of which have not yet been identified (Mengatto et al. 2011; Montes et al., 2007). Although some similarities between osseointegration and tooth extraction socket were seen, different pathways of transcription and growth factors, extracellular matrix molecules, and chemokines were proposed (Lin et al., 2010). A recent study with rats showed a possible network of genes that associated with success and failure of implant osseointegration (Mengatto et al., 2011). "

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