News Article | May 7, 2017
"It is truly inspiring to see how many community groups held bake sales, car washes and other fundraisers for this cause, and I want to challenge more of them to join our team," said Manning, who pledged to match the first $100,000 in fundraising from local community groups – which they exceeded in just a few short months. Five of the most innovative, creative and successful fundraising campaigns created by kids and community groups were honored, resulting in a check for $250,000 from "Eli's Challenge" to the Tackle Kids Cancer program, which benefitted from the New York Giants support. "We value our relationship with Hackensack University Medical Center and are honored to be part of Tackle Kids Cancer. The work that is done by the Children's Cancer Institute and those who have contributed to Tackle Kids Cancer has served as an inspiration to Eli and all of us," said Allison Stangeby, vice president of Community and Corporate Relations. "We are proud of Eli's work in our community and his selfless support of the Children's Cancer Institute." The event was part of NBC4 Telemundo Health Expo, Presented by Quest Diagnostics, which is held annually at MetLife Stadium welcoming a wide range of healthy lifestyle exhibits, as well as free health tests and screenings. "The Foundation is proud of the partnership we have with the New York Giants and its players," said Jon M. Fitzgerald, president of Hackensack University Medical Center Foundation. "Eli Manning's commitment to Tackle Kids Cancer has extended far beyond what we could have imagined. Not only has he volunteered to be the face of our campaign, but he has made numerous visits with the children, families and health care team at our Children's Cancer Institute. With Eli's Challenge, he has taken his role as champion of this cause to higher level, and we could not have raised more than $4 million for our Tackle Kids Cancer initiative without his support." The Children's Cancer Institute at Hackensack University Medical Center consists of dedicated clinicians and researchers specializing in pediatric cancer. With more than 100 active oncology and transplant clinical trials currently open, it is leading the charge to cure childhood cancer. "While extremely rare, pediatric cancer is the number one cause of death by disease in children in the U.S.," said Stephen Percy, M.D., interim chairman, Department of Pediatrics, Joseph M. Sanzari Children's Hospital. "Every dollar received through the Tackle Kids Cancer campaign will support our most important programs and research." ABOUT HACKENSACK MERIDIAN HEALTH Hackensack Meridian Health is a leading not-for-profit health care organization that is the most comprehensive and truly integrated health care network in New Jersey, offering a complete range of medical services, innovative research and life-enhancing care. Hackensack Meridian Health comprises 13 hospitals, including two academic medical centers, two children's hospitals and nine community hospitals, physician practices, more than 120 ambulatory care centers, surgery centers, home health services, long-term care and assisted living communities, ambulance services, lifesaving air medical transportation, fitness and wellness centers, rehabilitation centers, and urgent care and after-hours centers. Hackensack Meridian Health has 28,000 team members, more than 6,000 physicians and is a distinguished leader in health care philanthropy, committed to the health and well-being of the communities it serves. The Network's notable distinctions include having one of only five major academic medical centers in the nation to receive Healthgrades America's 50 Best Hospitals Award for five or more consecutive years, the number one hospital in New Jersey as ranked by U.S. News and World Report, consistently achieving Magnet® recognition for nursing excellence from the American Nurses Credentialing Center, recipient of the John M. Eisenberg Award for Patient Safety and Quality from The Joint Commission and the National Quality Forum, a six-time recipient of Fortune's "100 Best Companies to Work For," one of the "20 Best Workplaces in Health Care" in the nation, and the number one "Best Place to Work for Women." Hackensack Meridian Health is a member of AllSpire Health Partners, an interstate consortium of leading health systems, to focus on the sharing of best practices in clinical care and achieving efficiencies. The hospitals of Hackensack Meridian Health include: academic medical centers – Hackensack University Medical Center in Hackensack, Jersey Shore University Medical Center in Neptune; children's hospitals – Joseph M. Sanzari Children's Hospital in Hackensack, K. Hovnanian Children's Hospital in Neptune; community hospitals – Ocean Medical Center in Brick, Riverview Medical Center in Red Bank, Mountainside Medical Center in Montclair, Palisades Medical Center in North Bergen, Raritan Bay Medical Center in Perth Amboy, Southern Ocean Medical Center in Manahawkin, Bayshore Medical Center in Holmdel, Raritan Bay Medical Center in Old Bridge, and Pascack Valley Medical Center in Westwood. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/eli-manning-headlines-tackle-kids-cancer-all-stars-event-300452803.html
News Article | June 1, 2017
Hackensack Meridian Health is a pioneer in operationalizing bundled payments, participating in the Centers for Medicare & Medicaid Services' (CMS) Comprehensive Care for Joint Replacement (CJR) since the program launched in April 2016. He also contributed to white papers published by Medscape Medical News from the American Society of Clinical Oncology (ASCO) and OncLive summarizing the outcomes and savings bundled care and alternative payment models offer. "CMS is working to encourage the adoption of value-based care models specifically because of the potential for improved outcomes and lower costs. Achieving these goals will take time, but we have to do it if we truly want to fix healthcare," said Dr. Pecora. "I believe that in the not-so-distant future patients and doctors will have the information they need to choose the correct bundles and lanes that make the best sense. Patients achieve the best clinical outcomes when care is tailored to their individual needs, and the total cost of care should be less for the entire population." Dr. Pecora, who also attended the 2016 White House-sponsored Cancer Moonshot Summit in Washington, DC to accelerate cancer research, is widely acknowledged as one of the world's leading experts in blood and marrow stem cell transplantation, cellular medicine and immunology research. He has also been a leader in the establishment of Cancer Outcomes Tracking Analysis, known as COTA, a technology platform that improves clinical outcomes and reduces wasteful spend in oncology through precise classification of illness and a smarter use of data. "Our world class physicians at Hackensack Meridian Health are at the forefront of health care, driving research and innovation to create a new standard of care," said Robert C. Garrett, co-CEO, Hackensack Meridian Health. "As the chief of innovation and head of one of the largest cancer centers in the nation, Dr. Pecora will provide valuable insight at the Harvard Business School Summit about the impact value-based care will have on the health industry. The collaboration of health leaders in education, health care, technology, and business will help set an aggressive agenda for impacting global health." Dr. Pecora will participate in discussions at Harvard Business School with prominent members of the health industry and leaders in other fields including regional, national, public and private payers, employers, integrated payers and providers, pharma and device companies, and other industry thought leaders. Findings from Summit discussions will be included into a report that will be disseminated to stakeholders globally. ABOUT HACKENSACK MERIDIAN HEALTH Hackensack Meridian Health is a leading not-for-profit health care organization that is the most comprehensive and truly integrated health care network in New Jersey, offering a complete range of medical services, innovative research and life-enhancing care. Hackensack Meridian Health comprises 13 hospitals, including two academic medical centers, two children's hospitals and nine community hospitals, physician practices, more than 120 ambulatory care centers, surgery centers, home health services, long-term care and assisted living communities, ambulance services, lifesaving air medical transportation, fitness and wellness centers, rehabilitation centers, and urgent care and after-hours centers. Hackensack Meridian Health has 28,000 team members, more than 6,000 physicians and is a distinguished leader in health care philanthropy, committed to the health and well-being of the communities it serves. The Network's notable distinctions include having one of only five major academic medical centers in the nation to receive Healthgrades America's 50 Best Hospitals Award for five or more consecutive years, the number one hospital in New Jersey as ranked by U.S. News and World Report, consistently achieving Magnet® recognition for nursing excellence from the American Nurses Credentialing Center, recipient of the John M. Eisenberg Award for Patient Safety and Quality from The Joint Commission and the National Quality Forum, a six-time recipient of Fortune's "100 Best Companies to Work For," one of the "20 Best Workplaces in Health Care" in the nation, and the number one "Best Place to Work for Women." Hackensack Meridian Health is a member of AllSpire Health Partners, an interstate consortium of leading health systems, to focus on the sharing of best practices in clinical care and achieving efficiencies. The hospitals of Hackensack Meridian Health include: academic medical centers – Hackensack University Medical Center in Hackensack, Jersey Shore University Medical Center in Neptune; children's hospitals – Joseph M. Sanzari Children's Hospital in Hackensack, K. Hovnanian Children's Hospital in Neptune; community hospitals – Ocean Medical Center in Brick, Riverview Medical Center in Red Bank, Mountainside Medical Center in Montclair, Palisades Medical Center in North Bergen, Raritan Bay Medical Center in Perth Amboy, Southern Ocean Medical Center in Manahawkin, Bayshore Medical Center in Holmdel, Raritan Bay Medical Center in Old Bridge, and Pascack Valley Medical Center in Westwood. For additional information, please visit www.HackensackMeridianHealth.org. ABOUT THE JOHN THEURER CANCER CENTER AT HACKENSACK UNIVERSITY MEDICAL CENTER John Theurer Cancer Center at Hackensack University Medical Center is New Jersey's largest and most comprehensive center dedicated to the diagnosis, treatment, management, research, screenings, and preventive care as well as survivorship of patients with all types of cancers. The 14 specialized divisions covering the complete spectrum of cancer care have developed a close-knit team of medical, research, nursing, and support staff with specialized expertise that translates into more advanced, focused care for all patients. Each year, more people in the New Jersey/New York metropolitan area turn to the John Theurer Cancer Center for cancer care than to any other facility in New Jersey. Housed within a 775-bed not-for-profit teaching, tertiary care, and research hospital, the John Theurer Cancer Center provides state-of-the-art technological advances, compassionate care, research innovations, medical expertise, and a full range of aftercare services that distinguish the John Theurer Cancer Center from other facilities. For additional information, please visit www.jtcancercenter.org. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/hackensack-meridian-health-to-participate-in-harvard-business-school-summit-300466798.html
News Article | December 22, 2016
Over the past year, Dr. Isola his team has moved to a brand new, state of the art office. The newly constructed building is part of the Raritan Bay Medical Center. The building is beautiful; boasting five exam rooms, a larger office, two hygienists and brand new equipment. Since the big move, the office is using new office systems – they are now a fully digital, completely paperless office. Once patients fill out their paperwork, the information is then inputted into their system and shredded! There are no charts; even their appointment reminders are sent via text, email, and phone calls. Dr. Eugene Isola III, is a third generation dentist. His grandfather graduated from Tufts School of Dental Medicine in 1935. His father graduated from NYU School of Dentistry in 1965. 2015 celebrates 80 years for the Isola family being in dentistry as well as their commitment and passion to the Practice of Dentistry. Continuing the family practice will be Dr. Isola’s oldest son who is currently attending NYU School of Dentistry. Dr. Isola isn’t just a dentist – outside of the office, he’s an associate professor at Rutgers School of Dental Medicine. He also often partners with other practices in the building for various events. At a past event, Dr. Isola did a presentation at the Joslin Diabetes Center on how diabetes affects dental health. A standard of excellence in personalized dental care enables the practice to provide the quality dental services their patients deserve. They provide comprehensive treatment planning and use restorative and cosmetic dentistry to achieve their patients' optimal dental health. If a dental emergency occur, the practice makes every effort to see and care for a patient as soon as possible. As a practice, they are true believers that preventive care and education are the keys to optimal dental health. They strive to provide "dental health care" vs. "disease care". That's why they focus on thorough exams - checking the overall health of their patient's teeth and gums, performing oral cancer exams, and taking x-rays when necessary. They also know that routine cleanings, flossing, sealants, and fluoride are all helpful in preventing dental disease. Not only are they focused on the beauty of your smile, they're also concerned about their patients' oral health. Dr. Eugene Isola’s practice is conveniently located in Old Bridge, NJ. To learn more about Dr. Isola and to view his online profile, please follow the link below: http://www.njtopdocs.com/EugeneIsolaDDS About Us NJ Top Dentists is a comprehensive information resource of Top Doctors, Dentists and Hospitals. We are profiling over 900 Healthcare Providers and have made it convenient for you to find them. NJ Top Dentists allows patients to “meet” these providers online before making their appointment. You can also follow us on Facebook – Twitter – YouTube
News Article | February 15, 2017
SOMERVILLE, NJ--(Marketwired - Feb 14, 2017) - Brio Financial Group (BFG) today announced that Michael Losch has joined the Brio Financial Group as its Chief Operating Officer and will report directly to David Briones, Founder and Managing Member of Brio Financial Group based in Somerville, NJ, with satellite offices in New York, New York and Dallas, Texas. Mr. Briones said, "Brio's business has grown to the point where bringing an executive with Mike's experience on board is what we need to manage our growth successfully for our growing client list. The world of accounting and finance can be overwhelming for companies not equipped to deal with it and the Brio Financial Group is just the kind of entity that can work for smaller companies in the most cost effective manner." This is a newly created position within the Brio Financial Group as its business has grown to the point where it is important to build out its executive team with experienced professionals in the accounting and finance fields. Brio Financial Group provides hands on accounting and finance services to both public and private companies which are either early stage, seeking investments to get to the next level and/or requires support in a turnaround effort. Many businesses do not have access to the kind of higher level accounting and financial expertise Brio provides for a variety of reasons. Brio provides a solution to enable businesses to have the benefit of a top level professional accounting and finance team, but at a price point that is affordable. "I could not be more excited than to be joining the Brio team. Their professionalism and cost effective business model is exactly the kind of platform that is needed in the marketplace to assist our clients to meet their business goals," said Mike Losch. Prior to joining Brio Financial Group, Mike served as Chief Financial Officer, Secretary and Treasurer for entities as large as a Fortune 100 company and as small as startups seeking early stage funding. While at Tellium, Inc. the company grew from zero revenues to over $135 million in annual revenues, increased employees from 95 to over 550 and raised over $425 million including an IPO. At ACT Oncology, Inc. Mike was instrumental in establishing accounting and employee practices for the company as it doubled revenues annually, negotiated favorable contract terms with vendors/customers and the business increased its valuation fivefold. Mike worked with MSD Capital to close a $20 million convertible credit agreement on behalf of BioEnergy of America, Inc. that related to the construction of a biofuels plant on the east coast. As the culmination of an early twenty year career with Verizon, Inc. (formerly Bell Atlantic), Mike rose to Chief Financial Officer for Bell Atlantic-New Jersey. Prior to that assignment Mike served as the Executive Director Investor Relations for the Bell Atlantic Corporation at a time it was the world's third most widely held stock. Mike has been a board member for the Raritan Bay Medical Center (served as Treasurer and Chair of Audit Committee); the Eastern Monmouth Area Chamber of Commerce (served as Treasurer); President of the Shrewsbury Board of Education; Shrewsbury Youth Athletic Association (President and Treasurer), currently the Friendly Sons of St. Patrick of the Jersey Shore and the Big Brothers Big Sisters of Monmouth and Middlesex Counties. Mr. Losch received both a B. S. in Finance and an M.B.A. from Lehigh University and he has done post-graduate work at the Wharton School of Business and Williams College. Brio Financial Group is a forward-thinking, full-service financial consulting firm with a wealth of knowledge and experience in finance and public accounting. Since 2010, we have served over 75 companies as well as numerous banks, hedge funds, venture capital funds and private equity firms. We have earned a reputation for exceptional client service as a leading outsourced CFO and financial reporting firm. Our management team consists of six seasoned executives supported by a professional team with experience in finance, complex accounting and reporting, valuation, modeling and taxation. This provides our growing client list the expertise they need when they need it. For additional information on Brio Financial Group, visit www.briofinancial.com and connect with us on Twitter: @Brio_Financial
Antonescu C.R.,Sloan Kettering Cancer Center |
Le Loarer F.,Sloan Kettering Cancer Center |
Mosquera J..-M.,New York Medical College |
Sboner A.,New York Medical College |
And 11 more authors.
Genes Chromosomes and Cancer | Year: 2013
Conventional epithelioid hemangioendotheliomas (EHE) have a distinctive morphologic appearance and are characterized by a recurrent t(1;3) translocation, resulting in a WWTR1-CAMTA1 fusion gene. We have recently encountered a fusion-negative subset characterized by a somewhat different morphology, including focally well-formed vasoformative features, which was further investigated for recurrent genetic abnormalities. Based on a case showing strong transcription factor E3 (TFE3) immunoreactivity, fluorescence in situ hybridization (FISH) analysis for TFE3 gene rearrangement was applied to the index case as well as to nine additional cases, selected through negative WWTR1-CAMTA1 screening. A control group, including 18 epithelioid hemangiomas, nine pseudomyogenic HE, and three epithelioid angiosarcomas, was also tested. TFE3 gene rearrangement was identified in 10 patients, with equal gender distribution and a mean age of 30 years old. The lesions were located in somatic soft tissue in six cases, lung in three and one in bone. One case with available frozen tissue was tested by RNA sequencing and FusionSeq data analysis to detect novel fusions. A YAP1-TFE3 fusion was thus detected, which was further validated by FISH and reverse transcription polymerase chain reaction (RT-PCR). YAP1 gene rearrangements were then confirmed in seven of the remaining nine TFE3-rearranged EHEs by FISH. No TFE3 structural abnormalities were detected in any of the controls. The TFE3-rearranged EHEs showed similar morphologic features with at least focally, well-formed vascular channels, in addition to a variably solid architecture. All tumors expressed endothelial markers, as well as strong nuclear TFE3. In summary, we are reporting a novel subset of EHE occurring in young adults, showing a distinct phenotype and YAP1-TFE3 fusions. © 2013 Wiley Periodicals, Inc.
News Article | November 10, 2016
The International Association of HealthCare Professionals is pleased to welcome Homero G. Rivero, MD, Internist, to their prestigious organization with his upcoming publication in The Leading Physicians of the World. He is a highly trained and qualified internist with a vast expertise in all facets of his work. Dr. Rivero has been in practice for 30 years and is currently serving patients at his own private practice located in Miami, Florida. In addition, Dr. Rivero is on staff at Kendall Regional Medical Center in Miami, Florida, and Mercy Hospital in Miami, Florida. Dr. Rivero graduated with his Medical Degree in 1983 from the Instituto Superior de Ciencias Médicas de Villa Clara in Cuba. He then went on to complete his internship and residency training at the University of Medicine and Dentistry of New Jersey and Raritan Bay Medical Center in Old Bridge, New Jersey. Dr. Rivero holds board certification in Internal Medicine, and keeps current with the latest developments in his field through his professional membership with the American Medical Association. Additionally, he was honored as a Top Physician in 2012 and 2013, and when he is not assisting patients, Dr. Rivero enjoys traveling. Learn more about Dr. Rivero by reading his upcoming publication in The Leading Physicians of the World. FindaTopDoc.com is a hub for all things medicine, featuring detailed descriptions of medical professionals across all areas of expertise, and information on thousands of healthcare topics. Each month, millions of patients use FindaTopDoc to find a doctor nearby and instantly book an appointment online or create a review. FindaTopDoc.com features each doctor’s full professional biography highlighting their achievements, experience, patient reviews and areas of expertise. A leading provider of valuable health information that helps empower patient and doctor alike, FindaTopDoc enables readers to live a happier and healthier life. For more information about FindaTopDoc, visit:http://www.findatopdoc.com
News Article | November 16, 2016
On Monday, November 7, 2016, board-certified orthopedic spine surgeon Dr. Nasser Ani performed a minimally invasive anterior cervical discectomy and fusion (ACDF) surgery on a 56-year-old female patient who was experiencing severe arm pain and numbness. The surgery took place at the Metropolitan Surgical Institute, an outpatient surgical center in South Amboy, New Jersey. The patient was suffering from cervical radiculopathy, with symptoms of radiating arm pain, as a result of a severe disc herniation causing compression of the spinal nerve roots at levels C5-6 and C6-7. After failed conservative treatment including physical therapy and spine epidural injections, the patient elected to have a two-level anterior cervical discectomy and fusion. Dr. Ani utilized a minimally invasive surgery to address the patient’s cervical radiculopathy and disc herniation. He chose an anterior surgical approach to gain exposure to the cervical spine through a small transverse incision in the neck. Dr. Ani was able to remove the herniated discs, and free the compressed and pinched nerves. After the discectomy, Dr. Ani inserted SpineFrontier’s biocompatible LES ARENA-C (HA) cervical cages to restore natural disc height between the vertebral bodies using the Less Exposure Surgery (LES) technique and placed a low-profile, two-level LES INVUE MAX cervical plate on the operative levels to provide stability until fusion takes place. Dr. Ani commented on the case: “The LES INVUE plate, when paired with the LES ARENA-C (HA) interbody, was one of the safest, most efficient ways to stabilize this patient’s spine. The instruments and procedural steps are easy. The hydroxyapatite (HA) infused LES ARENA-C spacer, together with a cancellous bone sponge and the patient’s own stem cells will result in an excellent fusion.” Dr. Ani stated that “minimally invasive surgery enables patients to return home just hours after surgery with little to no pain. This patient will be able to return to work in two to three weeks.” Dr. Nasser Ani is a board-certified orthopedic and spine surgeon at Ani Medical Group, Orthopedic and Spine Institute of New Jersey and deals with all aspects of spinal disorders, deformities and scoliosis. Initially, patients are treated in a conservative fashion in an effort to provide pain relief and help them return to functional status. However, in some cases, when conservative treatments fails, surgical options are discussed as a means to return patients back to their normal daily living activities. Dr. Ani is affiliated with multiple hospitals in the area, including Bayshore Community Hospital, Riverview Medical Center, Raritan Bay Medical Center, and Monmouth Medical Center. He is also the Chief of Orthopedics at Bayshore Community Hospital. He received his medical degree from the American University of Beirut, Lebanon. He completed an orthopedic surgery and spine fellowship at McGill University in Montreal, Canada. Dr. Ani has been in practice for over 25 years, double boarded in the fields of orthopedics and spinal surgery, and holds several professional affiliations including the North American Spine Society, Fellow of the American Academy of Orthopedics Surgeons, Fellow of the American College of Surgeons, Fellow of the Royal College of Surgeons, American Society for Laser Medicine and Surgery, and the American Medical Association, just to name a few. About SpineFrontier® Inc. SpineFrontier Inc. (http://www.spinefrontier.com) is a growing medical technology company that designs, develops and markets both implants and instruments for spine surgery based on the Less Exposure Surgery (LES®) Philosophy. These technologies are designed to allow for outpatient surgery due to minimal disruption of normal tissues. SpineFrontier is headquartered in Malden, MA. It is a KICVentures portfolio company and the leader in LES® technologies and instruments. About Less Exposure Surgery Less Exposure Surgery (LES®) is based on a new philosophy of performing surgery. LES® is less invasive than MIS. By developing improved technologies and techniques tailored for pinpointing a problem and fixing it without collateral damage, LES® minimizes tissue disruption.
PubMed | Raritan Bay Medical Center, Rheumatology and Immunotherapy Center, Coeur dAlene Arthritis Clinic, Diablo Clinical Research and 3 more.
Type: Journal Article | Journal: Arthritis & rheumatology (Hoboken, N.J.) | Year: 2016
To assess joint disease activity by ultrasound (US) in patients with rheumatoid arthritis (RA) initiating treatment with adalimumab (ADA) plus methotrexate (MTX).Data for this post hoc analysis originated from the MUSICA trial (ClinicalTrials.gov identifier: NCT01185288), which evaluated the efficacy of initiating ADA (40 mg every other week) plus 7.5 or 20 mg/week MTX in 309 patients with RA with an inadequate response to MTX. Synovial vascularization over 24 weeks was assessed bilaterally at metacarpophalangeal joint 2 (MCP2), MCP3, MCP5, metatarsophalangeal joint 5, and the wrists by power Doppler US (PDUS). A semiquantitative 4-grade scale was used. Disease activity was assessed using the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) and Simplified Disease Activity Index (SDAI). The correlation between continuous variables was assessed using Pearsons correlation coefficient.After 24 weeks of treatment with ADA plus MTX, rapid improvements in the mean synovial vascularity score were observed; the greatest improvements were in MCP2 (-0.5), MCP3 (-0.4), and the wrist (-0.4). At week 24, patients with the lowest DAS28-CRP (<2.6) had the lowest mean 5-joint and 3-joint composite synovial vascularity scores. The 5-joint and 3-joint scores were strongly correlated (>0.9). Synovial vascularity scores correlated poorly with DAS28, swollen joint count in 66 joints (SJC66), SJC28, tender joint count in 68 joints (TJC68), TJC28, Clinical Disease Activity Index (CDAI), SDAI, physicians global assessment, patients global assessment of pain, and disease duration (<0.2). Thirty-two (70%) of 46 patients with a DAS28-CRP of <2.6, and 11 (58%) of 19 patients with an SDAI indicating remission had at least 1 joint with a synovial vascularity score of 1.PDUS detects changes in synovial vascularity in RA patients treated with ADA plus MTX, and residual synovial vascularity in patients in whom clinical disease control has been achieved.
Zhang Y.,University of Washington |
Zhang Y.,Raritan Bay Medical Center |
Otero J.E.,University of Iowa |
Abu-Amer Y.,University of Washington
Calcified Tissue International | Year: 2013
The transcription factor NF-κB family is central for osteoclastogenesis and inflammatory osteolysis. Activation of NF-κB dimers is regulated by a kinase complex predominantly containing IKKα (IKK1), IKKβ (IKK2), and a regulatory subunit, IKKγ/NEMO. IKKα and IKKβ catalyze the cytoplasmic liberation and nuclear translocation of various NF-κB subunits. The requirement of IKKα and IKKβ for normal bone homeostasis has been established. Congruently, mice devoid of IKKα or IKKβ exhibit in vitro and in vivo defects in osteoclastogenesis, and IKKβ-null mice are refractory to inflammatory arthritis and osteolysis. To better understand the molecular mechanism underlying IKKβ function in bone homeostasis and bone pathologies, we conducted structure-function analysis to determine IKKβ functional domains in osteoclasts. IKKβ encompasses several domains, of which the ubiquitination-like domain (ULD) has been shown essential for IKKβ activation. In this study, we examined the role of ULD in IKKβ-mediated NF-κB activation in osteoclast precursors and its contribution to osteoclastogenesis and osteolysis. We generated and virally introduced IKKβ in which the ULD domain has been deleted (IKKβ-ULD) into osteoclast progenitors. The results show that deletion of ULD diminishes IKKβ activity and that IKKβ-ULD strongly inhibits osteoclastogenesis. In addition, unlike wild type (WT)-IKKβ, IKKβ-ULD fail to restore RANKL-induced osteoclastogenesis by IKKβ-null precursors. Finally, we provide evidence that IKKβ-ULD blocks inflammatory osteolysis in a model of murine calvarial osteolysis. Thus, we identified the ULD as crucial for IKKβ activity and osteoclastogenesis and found that ULD-deficient IKKβ is a potent inhibitor of osteoclastogenesis and osteolysis. © 2013 Springer Science+Business Media New York.