Molecular Variations Related to the Regional Differences in Periosteal Growth at the Mandibular Ramus

Periosteal growth at human mandibular ramus is characterized by bone apposition at the posterior border and resorption at the anterior border. Molecular control of this regional variation is unclear. This study examined the expression of several molecules involved in bone apposition/resorption at these regions in vivo and in vitro. By using growing pigs as a model, the periosteal growth was assessed at the mandibular ramus by vital staining and histological observations. In parallel, periosteal tissues were harvested and pulverized for RNA and protein extraction. Periosteal cells were also isolated, expanded in osteogenic media, and subjected to a single dose of dynamic tensile strain (0, 5, or 10% magnitude at 0.5 Hz) to examine their responses to mechanical loading. Real‐time RT‐PCR and Western blot analyses were used to examine mRNA and protein expression from periosteal tissues and cultured cells. Histological observation confirmed an anterior‐resorption/posterior‐apposition pattern in the pig mandibular ramus. Both in vivo tissue and in vitro cells demonstrated greater mRNA expression of receptor activator of NF‐κB ligand (RANKL)/osteoprotegerin (OPG) ratio and bone morphogenetic protein 2 (BMP2) at the anterior region, while OPG expression at the anterior region was lower than the posterior region. In response to the application of a single dose of dynamic tensile strain, cultured periosteal cells appeared to change the expression profile of osteogenic markers but not that of RANKL/OPG and BMP2. These findings suggest that the unique regional variation of periosteal activity at the mandibular ramus is regulated by a differential expression of RANKL/OPG ratio (likely through differential induction of OPG) and BMP2. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.

[1]  B. Sarnat,et al.  Growth pattern of the pig mandible; a serial roentgenographic study using metallic implants. , 1955, The American journal of anatomy.

[2]  M. Engel,et al.  Reactive dyes as vital indicators of bone growth. , 1969, The American journal of anatomy.

[3]  S. Herring,et al.  The dynamics of mastication in pigs. , 1976, Archives of oral biology.

[4]  A. Grimm,et al.  “Silver dust”—a tool to study growth interrelationships between bone, periosteum and muscle , 1979, The Anatomical record.

[5]  A. Björk,et al.  Normal and abnormal growth of the mandible. A synthesis of longitudinal cephalometric implant studies over a period of 25 years. , 1983, European journal of orthodontics.

[6]  G. Carlsson,et al.  Gross anatomy of the mandibular joint and masticatory muscles in the domestic pig (Sus scrofa). , 1986, Archives of oral biology.

[7]  M. Cecchini,et al.  Macrophage colony stimulating factor restores in vivo bone resorption in the op/op osteopetrotic mouse. , 1990, Endocrinology.

[8]  A Longitudinal Radiographic Study of the Periosteal Migration along the Growing Rabbit Mandible , 1992, Journal of dental research.

[9]  M. Hans,et al.  Age-related differences in mandibular ramus growth: a histologic study. , 1995, The Angle orthodontist.

[10]  A. Wetterwald,et al.  Role of CSF‐1 in bone and bone marrow development , 1997, Molecular reproduction and development.

[11]  Brian R. Wong,et al.  TRANCE Is a Novel Ligand of the Tumor Necrosis Factor Receptor Family That Activates c-Jun N-terminal Kinase in T Cells* , 1997, The Journal of Biological Chemistry.

[12]  L. Lum,et al.  Evidence for a Role of a Tumor Necrosis Factor-α (TNF-α)-converting Enzyme-like Protease in Shedding of TRANCE, a TNF Family Member Involved in Osteoclastogenesis and Dendritic Cell Survival* , 1999, Journal of Biological Chemistry.

[13]  S. Morony,et al.  Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[14]  L. Lum,et al.  Evidence for a role of a tumor necrosis factor-alpha (TNF-alpha)-converting enzyme-like protease in shedding of TRANCE, a TNF family member involved in osteoclastogenesis and dendritic cell survival. , 1999, The Journal of biological chemistry.

[15]  R. Jilka,et al.  Essential Requirement of BMPs‐2/4 for Both Osteoblast and Osteoclast Formation in Murine Bone Marrow Cultures from Adult Mice: Antagonism by Noggin , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[16]  Keiji Naruse,et al.  Uniaxial cyclic stretch induces focal adhesion kinase (FAK) tyrosine phosphorylation followed by mitogen-activated protein kinase (MAPK) activation. , 2001, Biochemical and biophysical research communications.

[17]  B. Decallonne,et al.  An overview of real-time quantitative PCR: applications to quantify cytokine gene expression. , 2001, Methods.

[18]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[19]  R. Schmelzeisen,et al.  Making bone: implant insertion into tissue-engineered bone for maxillary sinus floor augmentation-a preliminary report. , 2003, Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery.

[20]  H. Hagiwara,et al.  Treatment of Myoblastic C2C12 Cells with BMP-2 Stimulates Vitamin D-induced Formation of Osteoclasts , 2003, Calcified Tissue International.

[21]  D. Heymann,et al.  Receptor activator of nuclear factor kappaB ligand (RANKL)/osteoprotegerin (OPG) ratio is increased in severe osteolysis. , 2003, The American journal of pathology.

[22]  David Haynes,et al.  Receptor activator NF kappaB ligand (RANKL) and osteoprotegerin (OPG) protein expression in periodontitis. , 2003, Journal of periodontal research.

[23]  Katsu Takahashi,et al.  Enhancement of bone volume in guided bone augmentation by cell transplants derived from periosteum: an experimental study in rabbit calvarium bone. , 2004, Clinical oral implants research.

[24]  S. Herring,et al.  Cranial sutures and bones: growth and fusion in relation to masticatory strain. , 2004, The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology.

[25]  B. Bay,et al.  Identification of RANKL in Osteolytic Lesions of the Facial Skeleton , 2004, Journal of dental research.

[26]  Di Chen,et al.  The BMP signaling and in vivo bone formation. , 2005, Gene.

[27]  P. Stern,et al.  Receptor activator of NF‐κB ligand protein expression in UMR‐106 cells is differentially regulated by parathyroid hormone and calcitriol , 2005, Journal of cellular biochemistry.

[28]  J. Heinrich,et al.  CSF-1, RANKL and OPG regulate osteoclastogenesis during murine tooth eruption. , 2004, Archives of oral biology.

[29]  Teiji Wada,et al.  RANKL-RANK signaling in osteoclastogenesis and bone disease. , 2006, Trends in molecular medicine.

[30]  T. Sugahara,et al.  Osteogenic potential of cultured human periosteum-derived cells - a pilot study of human cell transplantation into a rat calvarial defect model. , 2006, Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery.

[31]  Francesco Dell'Accio,et al.  Mesenchymal multipotency of adult human periosteal cells demonstrated by single-cell lineage analysis. , 2006, Arthritis and rheumatism.

[32]  J. Cornish,et al.  Deletion of Aspartate 182 in OPG Causes Juvenile Paget' Disease by Impairing Both Protein Secretion and Binding to RANKL , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[33]  S. Herring,et al.  Masticatory mechanics of a mandibular distraction osteogenesis site: interfragmentary micromovement. , 2007, Bone.

[34]  S. Shi,et al.  The miniature pig: a useful large animal model for dental and orofacial research. , 2007, Oral diseases.

[35]  L. Lanyon,et al.  Wnt/β-Catenin Signaling Is a Component of Osteoblastic Bone Cell Early Responses to Load-bearing and Requires Estrogen Receptor α* , 2007, Journal of Biological Chemistry.

[36]  S. Herring,et al.  Growing the Mandible: Role of the Periosteum and its Cells , 2007, Anatomical record.

[37]  P. Agius,et al.  Mechanical strain enhances extracellular matrix-induced gene focusing and promotes osteogenic differentiation of human mesenchymal stem cells through an extracellular-related kinase-dependent pathway. , 2007, Stem cells and development.

[38]  T. Young,et al.  Interactive effects of mechanical stretching and extracellular matrix proteins on initiating osteogenic differentiation of human mesenchymal stem cells , 2009, Journal of cellular biochemistry.

[39]  Yoshiaki Kawano,et al.  Mechano-transduction in Osteoblastic Cells Involves Strain-regulated Estrogen Receptor α-mediated Control of Insulin-like Growth Factor (IGF) I Receptor Sensitivity to Ambient IGF, Leading to Phosphatidylinositol 3-Kinase/AKT-dependent Wnt/LRP5 Receptor-independent Activation of β-Catenin Signaling , 2009, The Journal of Biological Chemistry.

[40]  M Yamaguchi,et al.  RANK/RANKL/OPG during orthodontic tooth movement. , 2009, Orthodontics & craniofacial research.

[41]  Alex Jacobson,et al.  Essentials of facial growth , 2009 .

[42]  J. Westendorf,et al.  Bone morphogenic protein 2 directly enhances differentiation of murine osteoclast precursors , 2010, Journal of cellular biochemistry.

[43]  Alan Wells,et al.  Epidermal Growth Factor (EGF) Treatment on Multipotential Stromal Cells (MSCs). Possible Enhancement of Therapeutic Potential of MSC , 2010, Journal of biomedicine & biotechnology.