Russell R Reid

University of Chicago, Chicago, Illinois, United States

Are you Russell R Reid?

Claim your profile

Publications (57)115.59 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Reconstructive solutions to cranial defects complicated by hostile sites (prior radiation, failed cranioplasty, or scalp, cranium or CSF infection) are essential to improve cerebral hemodynamics, metabolism and minimize neurological and psychological sequelae secondary to exposure.1This study compares autologous non-vascularized reconstruction with vascularized approaches to cranioplasty at hostile sites performed at our institution between 2003-2012. An approach to decision-making for reconstructing hostile cranial defects is also presented. Methods: This was an IRB approved retrospective chart review. Patients were segregated into three groups: 1) vascularized bone/free flap reconstructions (vascular group, n=14), 2) non-vascularized bone reconstructions (non-vascular group, n=13), and 3) non-vascularized bone/free-flap reconstructions (mixed group, n=8). Information was gathered on demographics (age, gender, reconstruction type, size of reconstruction, co-morbidities, pre-operative infection, open wound, radiation), and outcomes (surgical/medical complications, reconstructive failures). Comparisons were performed using ANOVA and Fisher exact tests with p<0.05 considered significant. Results: The vascular and mixed groups were more likely to be older (p=0.01), have greater history of open wound (p<0.001), and multiple failed cranioplasty (p=0.003) than the non-vascular group. The vascular and mixed groups had longer average hospital stays (p=0.0002) and more complications post-reconstruction (p=0.01) than the non-vascular group. The total flap failure rate was low, at 1, 1 and 0 respectively (p=NS). Conclusions:The three groups showed comparable rates of total flap failure, reoperation and successful achievement of cranial coverage post-reconstruction. This suggests that the surgeons selected appropriate repair approaches for the individual patients. We created the CRAnial Severity Score for Hostility (CRASSH) to assess operative site hostility by considering age, infection, defect size, tobacco use, pre-operative open wound, history of radiation, failed cranioplasty and/or CSF leak. We found a significant difference for high or low CRASSH in complication rate (p=0.01), surgical complication rate (p=0.04), a high correlation between high score and complication (0.46) and high score and surgical complication (0.54). Those with a high CRASSH were 7.8 times more likely to have complications (95% CI 1.56-38.8) and 12.8 times more likely to have surgical complications (95% CI 2.15-76.4), suggesting the need for more aggressive reconstructive approaches to maximally achieve long-term flap success.
    Plastic and reconstructive surgery. 10/2014; 134(4S-1 Suppl):18-19.
  • Source
    Maureen Beederman, Evan M. Farina, Russell R. Reid
    [Show abstract] [Hide abstract]
    ABSTRACT: The normal growth and development of the skull is a tightly regulated process that occurs along the osteogenic interfaces of the cranial sutures. Here, the borders of the calvarial bones and neighboring tissues above and below, function as a complex. Through coordinated remodeling efforts of bone deposition and resorption, the cranial sutures maintain a state of patency from infancy through early adulthood as the skull continues to grow and accommodate the developing brain’s demands for expansion. However, when this delicate balance is disturbed, a number of pathologic conditions ensue; and if left uncorrected, may result in visual and neurocognitive impairments. A prime example includes craniosynostosis, or premature fusion of one or more cranial and/or facial suture(s). At the present time, the only therapeutic measure for craniosynostosis is surgical correction by cranial vault reconstruction. However, elegant studies performed over the past decade have identified several genes critical for the maintenance of suture patency and induction of suture fusion. Such deeper understandings of the pathogenesis and molecular mechanisms that regulate suture biology may provide necessary insights toward the development of non-surgical therapeutic alternatives for patients with cranial suture defects. In this review, we discuss the intricate cellular and molecular interplay that exists within the suture among its three major components: dura mater, osteoblastic related molecular pathways and osteoclastic related molecular pathways.
    Genes & Diseases. 07/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The present study is a case report of a 3-year-old girl who was referred to our clinic with the clinical features of cherubism. A locally aggressive tumor was diffusely infiltrating the maxilla and mandible. At 4 years after resection, our patient has not demonstrated any signs of recurrence, which might point to a role for adjunctive chemotherapy, in this case imatinib (Gleevec), for odontogenic myxoma.
    Journal of Oral and Maxillofacial Surgery 06/2014; · 1.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Reconstruction of craniofacial defects in children presents several challenges that are not encountered in the adult population. Autologous bone grafts have long been the criterion standard for repairing these defects. Recently, several new materials and techniques have expanded our arsenal of reconstructive options. In this clinical report, we describe the use of both particulate bone grafting and demineralized bone matrix together to repair craniofacial defects encountered in pediatric patients.
    The Journal of craniofacial surgery 02/2014; · 0.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The reconstructive goals for myelodysplastic defects are to provide a multilayered, tension-free and well-vascularized closure to prevent cerebrospinal fluid leakage, wound infection or breakdown and to optimize neurologic outcomes. We reviewed our ten-year experience with myelodysplastic defects and our preferred technique for large defects utilizing paraspinous flaps followed by V-Y crescentic rotation advancement flaps. A retrospective chart review was performed on all myelodysplastic defects closed at the University of Chicago Medicine from 2002 to 2012. Twenty-three patients were treated: eight were closed using V-Y crescentic rotation advancement flaps, eight primarily, two with transposition flaps and five with bilateral latissimus dorsi and gluteus maximus myocutaneous flaps. Patient defect characteristics, reconstructive details, follow up time, and wound complications were analyzed. The primary closure group included eight patients. There was one minor complication and two major complications that required debridement and plastic surgery consultation in this group. The transposition group included two patients and had no wound healing issues. The latissimus and gluteus myocutaneous group included five patients and had one minor wound healing issues. The V-Y crescentic group included eight patients. There were four minor wound breakdowns in the lateral donor sites and one major wound complication involving a CSF leak, meningitis and wound breakdown that required debridement. The groups were stratified by size, <5 cm and >5 cm, and further analyzed. Bilateral V-Y crescentic rotation advancement flap is a useful option when confronted with large myelodysplastic defects. It provides a multilayer, tension-free wound closure and spares the gluteus maximus and latissimus dorsi muscle groups.
    Journal of Plastic Reconstructive & Aesthetic Surgery 01/2014; · 1.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: RNA interference (RNAi) denotes sequence-specific mRNA degradation induced by short interfering double-stranded RNA (siRNA) and has become a revolutionary tool for functional annotation of mammalian genes, as well as for development of novel therapeutics. The practical applications of RNAi are usually achieved by expressing short hairpin RNAs (shRNAs) or siRNAs in cells. However, a major technical challenge is to simultaneously express multiple siRNAs to silence one or more genes. We previously developed pSOS system, in which siRNA duplexes are made from oligo templates driven by opposing U6 and H1 promoters. While effective, it is not equipped to express multiple siRNAs in a single vector. Gibson DNA Assembly (GDA) is an in vitro recombination system that has the capacity to assemble multiple overlapping DNA molecules in a single isothermal step. Here, we developed a GDA-based pSOK assembly system for constructing single vectors that express multiple siRNA sites. The assembly fragments were generated by PCR amplifications from the U6-H1 template vector pB2B. GDA assembly specificity was conferred by the overlapping unique siRNA sequences of insert fragments. To prove the technical feasibility, we constructed pSOK vectors that contain four siRNA sites and three siRNA sites targeting human and mouse β-catenin, respectively. The assembly reactions were efficient, and candidate clones were readily identified by PCR screening. Multiple β-catenin siRNAs effectively silenced endogenous β-catenin expression, inhibited Wnt3A-induced β-catenin/Tcf4 reporter activity and expression of Wnt/β-catenin downstream genes. Silencing β-catenin in mesenchymal stem cells inhibited Wnt3A-induced early osteogenic differentiation and significantly diminished synergistic osteogenic activity between BMP9 and Wnt3A in vitro and in vivo. These findings demonstrate that the GDA-based pSOK system has been proven simplistic, effective and versatile for simultaneous expression of multiple siRNAs. Thus, the reported pSOK system should be a valuable tool for gene function studies and development of novel therapeutics.
    PLoS ONE 01/2014; 9(11):e113064. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The study is a case report on a three-year old girl who was referred to our clinic with the clinical features of cherubism. A locally aggressive tumor was diffusely infiltrating the maxilla and mandible. Our patient has not demonstrated any recurrence now 4 years post resection, which may point to a role of adjunctive chemotherapy, in this case imanitib (Gleevec), in odontogenic myxomas.
    Journal of Oral and Maxillofacial Surgery. 01/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Fibroblast growth factors (FGF) and their receptors serve many functions in both the developing and adult organism. Humans contain 18 FGF ligands and four FGF receptors (FGFR). FGF ligands are polypeptide growth factors that regulate several developmental processes including cellular proliferation, differentiation, and migration, morphogenesis, and patterning. FGF-FGFR signaling is also critical to the developing axial and craniofacial skeleton. In particular, the signaling cascade has been implicated in intramembranous ossification of cranial bones as well as cranial suture homeostasis. In the adult, FGFs and FGFRs are crucial for tissue repair. FGF signaling generally follows one of three transduction pathways: RAS/MAP kinase, PI3/AKT, or PLCγ. Each pathway likely regulates specific cellular behaviors. Inappropriate expression of FGF and improper activation of FGFRs are associated with various pathologic conditions, unregulated cell growth, and tumorigenesis. Additionally, aberrant signaling has been implicated in many skeletal abnormalities including achondroplasia and craniosynostosis. The biology and mechanisms of the FGF family have been the subject of significant research over the past 30 years. Recently, work has focused on the therapeutic targeting and potential of FGF ligands and their associated receptors. The majority of FGF-related therapy is aimed at age-related disorders. Increased understanding of FGF signaling and biology may reveal additional therapeutic roles, both in utero and postnatally. This review discusses the role of FGF signaling in general physiologic and pathologic embryogenesis and further explores it within the context of skeletal development.
    Genes & Diseases. 01/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The psychosocial impact of craniofacial disfigurement affects both the developing child and his/her family. The Facial Reconstruction Center at the Children's Hospital of Philadelphia has employed a Parent Liaison (PL) to provide psychosocial support to families and has been an invaluable resource in this regard. We hypothesize that a PL impacts the overall outcome of the surgery by building trust between the parents and medical institution, and increasing satisfaction. An anonymous satisfaction survey was sent to families of craniofacial patients treated between January 1976 and June 2012. All patients who had undergone at least 1 craniofacial procedure had addresses on file and were included in this study. Statistical analyses were performed using the Mann-Whitney U test.During the study, 441 surveys were mailed to families meeting the inclusion criteria. A total of 151 families returned completed surveys (34.2%), and 121 surveys were included for analysis (27.4%). In rating overall satisfaction, families who met with the PL had statistically higher scores than those who had not (P = 0.0011). Parents who met with the PL preoperatively reported greater satisfaction in time spent answering questions (P = 0.0029) and the perception that questions were adequately answered (P = 0.0039). No statistical difference was observed in postoperative preparedness between families that did and did not meet the PL. The results demonstrate that the PL is beneficial in the education, experience, and satisfaction of families treated at a large Craniofacial Center. The PL complements the surgeon's treatment of the physical by adding psychosocial support.
    The Journal of craniofacial surgery 11/2013; 24(6):1898-901. · 0.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Composite cranial defects in the setting of infection, irradiation, or cerebrospinal fluid leak present a significant risk for devastating neurologic sequelae. Such defects require soft-tissue coverage and skeletal reconstruction that can withstand the hostile environment of a precarious wound. Patients with high-risk composite cranial defects treated with free flap reconstruction containing a vascularized osseous component from 2003 to 2012 were reviewed retrospectively. Fourteen patients received autologous vascularized cranioplasties between 2003 and 2012 with a mean age of 55.7 years and a mean follow-up of 14.1 months. Preoperatively, all patients had infection, irradiation, cerebrospinal fluid leak, or a combination thereof. Thirteen patients (92.9 percent) were reoperative cases for recurrent tumor, infection, or both. Six patients (42.9 percent) failed previous reconstructive procedures. Tissue biopsy-proven infection was present in 10 patients (71.4 percent) with calvarial osteomyelitis, both osteomyelitis and meningitis, or scalp soft-tissue infection only. Nine patients (64.3 percent) suffered from malignancy and six of these patients were irradiated preoperatively. Cranioplasty was achieved as part of a chimeric free flap using rib, scapula, both rib and scapula, or ilium. Vascularized duraplasty using serratus anterior fascia as a component of the chimeric flap was performed in three patients. No flap losses occurred and all patients had resolution of infection. Soft-tissue and skeletal restoration are the two critical components of composite cranial reconstruction. The authors report outcomes of the largest series of one-stage immediate cranioplasty consisting of autologous soft tissue and vascularized bone in high-risk composite cranial wounds and suggest its application in defects associated with compromised wound beds. Therapeutic, IV.
    Plastic and reconstructive surgery 10/2013; 132(4):967-75. · 2.74 Impact Factor
  • Jonathan Bank, Kelly J Ledbetter, Russell R Reid
    The Journal of craniofacial surgery 05/2013; 24(3):1054-1055. · 0.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The RUNX2 transcription factor regulates osteoblast differentiation. Its absence, as with cleidocranial dysplasia, results in deficient bone formation. However, its excess seems to follow a dose response of over ossification. RUNX2 duplications (3 copies) are exceedingly rare but have been reported to cause craniosynostosis. There are no existing reports of quadruplications (4 copies). We present a case study of a boy with an atypical skull deformity with pan-craniosynostosis whose microarray analysis revealed 4 copies of a 1.24-Mb region from 6p12.3 to 6p21.1 containing the RUNX2 gene. Further characterization of this osteogenic pathway may aid in our understanding of the pathogenesis and subsequent prevention and treatment of syndromic craniosynostosis.
    The Journal of craniofacial surgery 01/2013; 24(1):126-9. · 0.81 Impact Factor
  • Rina Patel, Russell R Reid, Colin S Poon
    [Show abstract] [Hide abstract]
    ABSTRACT: Maxillofacial fractures are very common. Recognizing patterns of facial fractures is helpful in assessing maxillofacial injury and accurately characterizing all fractures that may be present. Facial fractures are grouped into the following categories: nasal bone, naso-orbito-ethmoid, orbital, zygomatic, maxillary (including Le Fort-type fractures), mandibular, and frontal sinus fractures. Within each subgroup of facial fractures, there are key findings, whether of the fracture itself or of potential associated injuries, that are important factors in determining whether the patient is managed conservatively or with surgery. This article highlights the features of facial fractures that are the most important to the surgeons and provides a framework for effective radiological reporting.
    Seminars in ultrasound, CT, and MR. 10/2012; 33(5):410-7.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The squamosal suture is markedly different from the major calvarial sutures of the human skull. The unique properties of the suture are a result of the complex developmental biology of the temporal bone and biomechanical force exerted by surrounding structures. The dysmorphic effects of premature fusion of the suture, and possible treatment strategies in cases of synostosis, have received only brief description in the literature. A retrospective case series was performed. The study included patients evaluated by one of the senior authors (S.P.B., R.R.R., and D.J.S.) between 1993 and 2009. All pertinent patient data including inpatient and outpatient charts, photographic records, and radiographic scans were reviewed. Any management performed under the direction of a craniofacial surgeon was documented--including orthotic helmet therapy and operative management. The study included 14 patients. Synostosis of the squamosal suture was noted to occur either in an isolated fashion or in the setting of other craniofacial malformations. Patients with isolated squamosal synostosis often suffered from a deformity that was mild in severity and tended to improve with time. However, when occurring in the setting of other forms of craniosynostosis, the deformity was often progressive, and transcranial surgery was frequently required. Synostosis of the squamosal suture can result in, or contribute to, significant craniofacial dysmorphism. The optimal form of therapy for this disorder is evolving.
    Plastic and reconstructive surgery 03/2012; 130(1):165-76. · 2.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Craniofacial defect repair is often limited by a finite supply of available autologous tissue (ie, bone) and less than ideal alternatives. Therefore, other methods to produce bony healing must be explored. Several studies have demonstrated that low-frequency pulsed electromagnetic field (PEMF) stimulation (ie, 5-30 Hz) of osteoblasts enhances bone formation. The current study was designed to investigate whether a Food and Drug Administration-approved, high-frequency PEMF-emitting device is capable of inducing osteogenic differentiation of osteoprogenitor cells. Osteoprogenitor cells (commercially available C3H10T1/2 and mouse calvarial) in complete Dulbecco modified Eagle medium were continuously exposed to PEMF stimulation delivered by the ActiPatch at a frequency of 27.1 MHz. Markers of cellular proliferation and early, intermediate, and terminal osteogenic differentiation were measured and compared with unstimulated controls. All experiments were performed in triplicate. High-frequency PEMF stimulation increases alkaline phosphatase activity in both cell lines. In addition, high-frequency PEMF stimulation augments osteopontin and osteocalcin expression as well as mineral nodule formation in C3H10T1/2 cells, indicating late and terminal osteogenic differentiation, respectively. Cellular proliferation, however, was unaffected by high-frequency PEMF stimulation. Mechanistically, high-frequency PEMF-stimulated osteogenic differentiation is associated with elevated mRNA expression levels of osteogenic bone morphogenetic proteins in C3H10T1/2 cells. Our findings suggest that high-frequency PEMF stimulation of osteoprogenitor cells may be explored as an effective tissue engineering strategy to treat critical-size osseous defects of the craniofacial and axial skeleton. ABBREVIATIONS: ALP, alkaline phosphatase; BMP, bone morphogenetic protein; ERK-1, extracellular signal-regulated kinase 1; iCALs, immortalized calvarial cells; IHC, immunohistochemical; MAP, mitogen-activated protein; MSC, mesenchymal stem cell; OCN, osteocalcin; OPN, osteopontin; p38α, p38-reactivating kinase; PBS, phosphate-buffered saline; PEMF, pulsed electromagnetic field.
    The Journal of craniofacial surgery 03/2012; 23(2):586-93. · 0.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Critical-size osseous defects cannot heal without surgical intervention and can pose a significant challenge to craniofacial reconstruction. Autologous bone grafting is the gold standard for repair but is limited by a donor site morbidity and a potentially inadequate supply of autologous bone. Alternatives to autologous bone grafting include the use of alloplastic and allogenic materials, mesenchymal stem cells, and bone morphogenetic proteins. Bone morphogenetic proteins (BMPs) are essential mediators of bone formation involved in the regulation of differentiation of osteoprogenitor cells into osteoblasts. Here we focus on the use of BMPs in experimental models of craniofacial surgery and clinical applications of BMPs in the reconstruction of the cranial vault, palate, and mandible and suggest a model for the use of BMPs in personalized stem cell therapies.
    BioMed Research International 01/2012; 2012:601549. · 2.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mesenchymal stem cells (MSCs) are multipotent cells which reside in many tissues and can give rise to multiple lineages including bone, cartilage and adipose. Although MSCs have attracted significant attention for basic and translational research, primary MSCs have limited life span in culture which hampers MSCs' broader applications. Here, we investigate if mouse mesenchymal progenitors can be conditionally immortalized with SV40 large T antigen and maintain long-term cell proliferation without compromising their multipotency. Using the system which expresses SV40 large T antigen flanked with Cre/loxP sites, we demonstrate that mouse embryonic fibroblasts (MEFs) can be efficiently immortalized by SV40 large T antigen. The conditionally immortalized MEFs (iMEFs) exhibit an enhanced proliferative activity and maintain long-term cell proliferation, which can be reversed by Cre recombinase. The iMEFs express most MSC markers and retain multipotency as they can differentiate into osteogenic, chondrogenic and adipogenic lineages under appropriate differentiation conditions in vitro and in vivo. The removal of SV40 large T reduces the differentiation potential of iMEFs possibly due to the decreased progenitor expansion. Furthermore, the iMEFs are apparently not tumorigenic when they are subcutaneously injected into athymic nude mice. Thus, the conditionally immortalized iMEFs not only maintain long-term cell proliferation but also retain the ability to differentiate into multiple lineages. Our results suggest that the reversible immortalization strategy using SV40 large T antigen may be an efficient and safe approach to establishing long-term cell culture of primary mesenchymal progenitors for basic and translational research, as well as for potential clinical applications.
    PLoS ONE 01/2012; 7(2):e32428. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose Craniofacial defects, whether due to trauma, tumor, or congenital disease, pose challenging problems to reconstructive surgeons. In many clinical scenarios, autologous tissue is simply not enough, forcing the reconstructive surgeon to repair the defect with alloplastic materials, which do not incorporate into local tissues and therefore can fail over time. These challenges therefore require the investigation of novel strategies to regenerate bony tissue. To this end, we have demonstrated that the delivery of high-frequency pulsed electromagnetic fields (PEMFs) through a novel device accelerates osteogenic differentiation of murine osteoprogenitor cells. Methods and Materials Murine osteoprogenitor cells (C3H10T1/2) and cells harvested from the calvaria of 21-day old CD-1 miceHHfrlkjdf were stimulated by the ActiPatch(TM) (BioElectronics, Frederick, MD) for 14 days (24 h/day). The nominal carrier frequency delivered by the ActiPatch(TM) is 27.1 MHz. Markers of cellular proliferation and early, intermediate and terminal osteogenic differentiation were measured and compared to unstimulated controls. Results Alkaline phosphatase (ALP) activity, an early marker of osteogenic differentiation, was significantly elevated in PEMF-stimulated C3H10T1/2 cells and primary calvarial cells at multiple time points throughout the duration of the study (Figure 1). In addition, stimulated C3H10T1/2 cells expressed increased mRNA transcript levels of osteocalcin, MAP kinase, and BMP-2, -4, -6, -7, and -9. Stimulated C3H10T1/2 cells also displayed increased osteocalcin and osteopontin protein expression as assessed by immunohistochemistry. Both C3H10T1/2 and primary calvarial cells that underwent PEMF stimulation displayed increased bone nodule formation at day 14 via alizarin Red S staining (Figure 2). PEMF stimulation did not induce alterations of cellular proliferation patterns in either cell line. Conclusion We have demonstrated that a novel delivery system of high-frequency PEMFs is capable of accelerating osteoprogenitor cell differentiation into bone. Our findings evoke future experiments to address the cell-specific response to this form of biophysical stimulation, the mechanism underlying high-frequency PEMF stimulation, and the potential role of this device for in vivo bone tissue engineering. Figure 1. Alkaline phosphatase (ALP) activity in stimulated and unstimulated C3H10T1/2 and primary calvarial cells. ALP activity was measured at 3, 5, 7, 9, and 12 days after the initiation of PEMF stimulation. Figure 2. Alizarin red S staining of stimulated and unstimulated C3H10T1/2 and primary calvarial cells. Staining was performed 14 days after initiation of PEMF stimulation.
    Plastic Surgery: The Meeting 2011; 09/2011
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Promoting osteogenic differentiation and efficacious bone regeneration have the potential to revolutionize the treatment of orthopaedic and musculoskeletal disorders. Mesenchymal Stem Cells (MSCs) are bone marrow progenitor cells that have the capacity to differentiate along osteogenic, chondrogenic, myogenic, and adipogenic lineages. Differentiation along these lineages is a tightly controlled process that is in part regulated by the Bone Morphogenetic Proteins (BMPs). BMPs 2 and 7 have been approved for clinical use because their osteoinductive properties act as an adjunctive treatment to surgeries where bone healing is compromised. BMP-9 is one of the least studied BMPs, and recent in vitro and in vivo studies have identified BMP-9 as a potent inducer of osteogenic differentiation in MSCs. BMP-9 exhibits significant molecular cross-talk with the Wnt/ β-catenin and other signaling pathways, and adenoviral expression of BMP-9 in MSCs increases the expression of osteogenic markers and induces trabecular bone and osteiod matrix formation. Furthermore, BMP-9 has been shown to act synergistically in bone formation with other signaling pathways, including Wnt/ β-catenin, IGF, and retinoid signaling pathways. These results suggest that BMP-9 should be explored as an effective bone regeneration agent, especially in combination with adjuvant therapies, for clinical applications such as large segmental bony defects, non-union fractures, and/or spinal fusions.
    Current Gene Therapy 04/2011; 11(3):229-40. · 5.32 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Craniosynostosis is a significant disorder affecting 1 in 2500 live births worldwide. Although a large body of work has focused on dural regulation and the contributions of molecular mediators such as fibroblast growth factor, bone morphogenetic protein, and transforming growth factor β, minimal attention has been directed toward osteoclast function in cranial suture biology. Receptor activator of nuclear factor κB (RANK) is an essential mediator of osteoclastogenesis and osteoclast activation. In this study, physiologic fusion of posterior frontal sutures in murine development correlated with decreasing protein expression of RANK in comparison to age-matched coronal and sagittal sutures via immunohistochemical survey. However, RANK mRNA did not exhibit a similar pattern suggesting that RANK is regulated at the protein level. Fused cranial sutures in nonsyndromic craniosynostotic children also showed decreased levels of RANK staining in immunohistochemistry in comparison to patent sutures from the same patients. Immunohistochemistry with a RANK ligand antibody did not show differences in fused or patent sutures. Moreover, RANK knockdown in calvarial strip suture cultures displayed increased bone density specifically in the suture line after infection with small interfering RANK viruses. Cranial suture biology, similar to bone biology in general, likely depends on a complex interplay between osteoblasts and osteoclasts. We now report a temporospatial correlation between RANK expression and suture morphology that suggests that osteoclast activity is important in maintenance of cranial suture patency in normal physiology and disease. Furthermore, RANK downregulation promoted suture fusion establishing a causal relationship between the presence of RANK and patency.
    The Journal of craniofacial surgery 03/2011; 22(2):699-705. · 0.81 Impact Factor

Publication Stats

756 Citations
115.59 Total Impact Points


  • 2008–2014
    • University of Chicago
      • • Specialty of Plastic and Reconstructive Surgery
      • • Department of Surgery
      Chicago, Illinois, United States
    • Chongqing Medical University
      Ch’ung-ch’ing-shih, Chongqing Shi, China
  • 2007–2014
    • The University of Chicago Medical Center
      • • Section of Plastic and Reconstructive Surgery
      • • Department of Surgery
      Chicago, Illinois, United States
    • Hospital of the University of Pennsylvania
      • Division of Plastic Surgery
      Philadelphia, Pennsylvania, United States
    • Georgetown University
      Washington, Washington, D.C., United States
  • 2012
    • Chongqing University
      • School of Bioengineering
      Chongqing, Chongqing Shi, China
  • 2007–2012
    • The Children's Hospital of Philadelphia
      Philadelphia, Pennsylvania, United States
  • 2004–2007
    • Northwestern University
      • • Division of Plastic Surgery
      • • Feinberg School of Medicine
      Evanston, IL, United States