The Future of Dental Schools in Research Universities and Academic Health Centers

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153596/1/jddjde017039.pd

Twenty‐five years of PTHrP progress: From cancer hormone to multifunctional cytokine

Twenty‐five years ago a “new” protein was identified from cancers that caused hypercalcemia. It was credited for its ability to mimic parathyroid hormone (PTH), and hence was termed parathyroid hormone‐related protein (PTHrP). Today it is recognized for its widespread distribution, its endocrine, paracrine, and intracrine modes of action driving numerous physiologic and pathologic conditions, and its central role in organogenesis. The multiple biological activities within a complex molecule with paracrine modulation of adjacent target cells present boundless possibilities. The protein structure of PTHrP has been traced, dissected, and deleted comprehensively and conditionally, yet numerous questions lurk in its past that will carry into the future. Issues of the variable segments of the protein, including the enigmatic nuclear localization sequence, are only recently being clarified. Aspects of PTHrP production and action in the menacing condition of cancer are emerging as dichotomies that may represent intended temporal actions of PTHrP. Relative to PTH, the hormone regulating calcium homeostasis, PTHrP “controls the show” locally at the PTH/PTHrP receptor throughout the body. Great strides have been made in our understanding of PTHrP actions, yet years of exciting investigation and discovery are imminent. © 2012 American Society for Bone and Mineral Research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91351/1/1617_ftp.pd

Mediators of Periodontal Osseous Destruction and Remodeling: Principles and Implications for Diagnosis and Therapy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142298/1/jper1377.pd

Synthesis and Erosion Properties of PEG-Containing Polyanhydrides

To tailor the erosion rate of polyanhydrides while retaining their surface erosion characteristics, new three-component polyanhydrides of sebacic acid, 1,3-bis( p -carboxyphenoxy)propane and poly(ethylene glycol) were synthesized. The hydrophilicity of the polymer increased and its mechanical strength decreased with increasing PEG content. Correspondingly, the erosion rate increases with increasing PEG content, whereas it decreases with increasing specimen thickness. This indicates that the incorporation of poly(ethylene glycol) into traditional two-component polyanhydrides retains their surface erosion properties while making the erosion rate tunable. The new polyanhydrides hold potential for drug delivery applications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56103/1/620_ftp.pd

Delivery Device and Method for Forming the Same

A delivery device includes a hollow container, and a plurality of biodegradable and/or erodible polymeric layers established in the container. A layer including a predetermined substance is established between each of the plurality of polymeric layers, whereby degradation of the polymeric layer and release of the predetermined substance occur intermittently. Methods for forming the device are also disclosed herein

Modulation of Osteoblastic Cell Efferocytosis by Bone Marrow Macrophages

Apoptosis occurs at an extraordinary rate in the human body and the effective clearance of dead cells (efferocytosis) is necessary to maintain homeostasis and promote healing, yet the contribution and impact of this process in bone is unclear. Bone formation requires that bone marrow stromal cells (BMSCs) differentiate into osteoblasts which direct matrix formation and either become osteocytes, bone lining cells, or undergo apoptosis. A series of experiments were performed to identify the regulators and consequences of macrophage efferocytosis of apoptotic BMSCs (apBMSCs). Bone marrow derived macrophages treated with the anti‐inflammatory cytokine interleukin‐10 (IL‐10) exhibited increased efferocytosis of apBMSCs compared to vehicle treated macrophages. Additionally, IL‐10 increased anti‐inflammatory M2‐like macrophages (CD206+), and further enhanced efferocytosis within the CD206+ population. Stattic, an inhibitor of STAT3 phosphorylation, reduced the IL‐10‐mediated shift in M2 macrophage polarization and diminished IL‐10‐directed efferocytosis of apBMSCs by macrophages implicating the STAT3 signaling pathway. Cell culture supernatants and RNA from macrophages co‐cultured with apoptotic bone cells showed increased secretion of monocyte chemotactic protein 1/chemokine (C‐C motif) ligand 2 (MCP‐1/CCL2) and transforming growth factor beta 1 (TGF‐β1) and increased ccl2 gene expression. In conclusion, IL‐10 increases M2 macrophage polarization and enhances macrophage‐mediated engulfment of apBMSCs in a STAT3 phosphorylation‐dependent manner. After engulfment of apoptotic bone cells, macrophages secrete TGF‐β1 and MCP‐1/CCL2, factors which fuel the remodeling process. A better understanding of the role of macrophage efferocytosis as it relates to normal and abnormal bone turnover will provide vital information for future therapeutic approaches to treat bone related diseases. J. Cell. Biochem. 117: 2697–2706, 2016. © 2016 Wiley Periodicals, Inc.The process of efferocytosis (clearance of apoptotic cells) has been characterized in various tissues but the role of efferocytosis in the bone microenvironment is unclear. Bone marrow macrophage efferocytosis of apoptotic osteoblastic cells was enhanced by interleukin‐10 in a STAT‐3 dependent manner and resulted in increased production of TGF‐β1 and CCL‐2. The process of efferocytosis is likely important in bone remodeling and osseous wound healing.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134491/1/jcb25567.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134491/2/jcb25567_am.pd

Mentoring of Dental and Dental Hygiene Faculty: A Case Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153712/1/jddj002203372011753tb05042x.pd

Immune mediators in the tumor microenvironment of prostate cancer

Prostate cancer tissue is composed of both cancer cells and host cells. The milieu of host components that compose the tumor is termed the tumor microenvironment (TME). Host cells can be those derived from the tissue in which the tumor originates (e.g., fibroblasts and endothelial cells) or those recruited, through chemotactic or other factors, to the tumor (e.g., circulating immune cells). Some immune cells are key players in the TME and represent a large proportion of non‐tumor cells found within the tumor. Immune cells can have both anti‐tumor and pro‐tumor activity. In addition, crosstalk between prostate cancer cells and immune cells affects immune cell functions. In this review, we focus on immune cells and cytokines that contribute to tumor progression. We discuss T‐regulatory and T helper 17 cells and macrophages as key modulators in prostate cancer progression. In addition, we discuss the roles of interleukin‐6 and receptor activator of nuclear factor kappa‐B ligand in modulating prostate cancer progression. This review highlights the concept that immune cells and cytokines offer a potentially promising target for prostate cancer therapy.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152631/1/cac2s4088001701983.pd

Accuracy and Consistency of Radiographic Interpretation Among Clinical Instructors in Conjunction with a Training Program

There are inaccuracies and inconsistencies of radiographic interpretation among clinical instructors. The purpose of this investigation was to determine if a training program could improve the accuracy and consistency of instructors’ ratings of bone loss. A total of thirty-five clinical instructors consisting of periodontal faculty (periodontists and general dentists), dental hygiene faculty, and periodontal graduate students viewed projected digitized radiographic images and quantified bone loss for twenty-five teeth into four descriptive categories. Ratings of bone loss were made immediately before (pretest) and after (post-test 1) initiation of the training program and then again three months later (post-test 2). Ratings were compared to the correct choice categories as determined by direct measurement using the Schei ruler. Overall agreement with the correct choice improved over time (from 64.5 percent to 85.2 percent) with the greatest change from pretest (64.5 percent) to post-test 1 (76.5 percent). Mean and absolute differences improved in three of the four categories, but worsened in one from pretest to post-test 1. This category returned to its original high value at post-test 2. The greatest improvement in consistency among instructors’ ratings was seen in one of the four categories, which was “none” (no bone loss). Extension of the training program may further enhance the accuracy and consistency of instructors’ radiographic interpretation

Accuracy and Consistency of Radiographic Interpretation Among Clinical Instructors Using Two Viewing Systems

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153540/1/jddj002203372006702tb04071x.pd