Musculoskeletal Diseases Commons^™

Srebp2 Restricts Osteoclast Differentiation And Activity By Regulating Irf7 And Limits Inflammatory Bone Erosion, Haemin Kim, In Ah Choi, Akio Umemoto, Seyeon Bae, Kaichi Kaneko, Masataka Mizuno, Eugenia Giannopoulou, Tania Pannellini, Liang Deng, Kyung-Hyun Park-Min

Publications and Research

Osteoclasts are multinucleated bone-resorbing cells, and their formation is tightly regulated to prevent excessive bone loss. However, the mechanisms by which osteoclast formation is restricted remain incompletely determined. Here, we found that sterol regulatory element binding protein 2 (SREBP2) functions as a negative regulator of osteoclast formation and inflammatory bone loss. Cholesterols and SREBP2, a key transcription factor for cholesterol biosynthesis, increased in the late phase of osteoclastogenesis. The ablation of SREBP2 in myeloid cells resulted in increased in vivo and in vitro osteoclastogenesis, leading to low bone mass. Moreover, deletion of SREBP2 accelerated inflammatory bone destruction in murine inflammatory …

A Bisphosphonate With A Low Hydroxyapatite Binding Affinity Prevents Bone Loss In Mice After Ovariectomy And Reverses Rapidly With Treatment Cessation, Abigail A. Coffman, Jelena Basta-Pljakic, Rosa M. Guerra, Frank H. Ebetino, Mark W. Lundy, Robert J. Majeska, Mitchell B. Schaffler

Publications and Research

Bisphosphonates (BPs) are a mainstay of osteoporosis treatment; however, concerns about bone health based on oversuppression of remodeling remain. Long-term bone remodeling suppression adversely affects bone material properties with microdamage accumulation and reduced fracture toughness in animals and increases in matrix mineralization and atypical femur fractures in patients. Although a “drug holiday” from BPs to restore remodeling and improve bone quality seems reasonable, clinical BPs have long functional half-lives because of their high hydroxyapatite (HAP) binding affinities. This places a practical limit on the reversibility and effectiveness of a drug holiday. BPs with low HAP affinity and strong osteoclast inhibition …

Restoration Of Bone Material And Microstructural Properties After Long-Term Remodeling Suppression, Abigail A. Coffman

Dissertations and Theses

Anti-resorptive drugs, principally bisphosphonates (BPs), are the mainstay of osteoporosis treatment. They work by inhibiting bone resorption/remodeling, thus preventing bone loss. However, long-term suppression of bone resorption adversely affects bone tissue mechanical properties, even while conserving bone mass. Lack of remodeling leads to accumulation of fatigue-induced microdamage, altered matrix mineralization and reduction in normal bone tissue heterogeneity, causing impaired strength and fracture toughness. The most severe consequence to patients, while rare, is Atypical Femur Fractures (i.e., complete fatigue fractures of the femoral shaft). To counteract the effects of long-term remodeling suppression, a temporary break in BP treatment (a "drug holiday) …

Characterization Of Bone Pathology In Sickle Cell Disease And Therapeutic Strategies, Mykel D. Green

Dissertations and Theses

Sickle cell disease (SCD) is a genetic hemoglobinopathy that has grown into a global health concern. While the advances in medical treatment and management of SCD during childhood have drastically improved the overall survival of children, the transition from pediatric to adult services is significantly inadequate in comparison. Life expectancies of patients with SCD in first world countries such as the United States are shortened to averages of 42 and 48 years for men and women, respectively. Despite the increasing number of people living with SCD, remarkably, few detailed studies have described the clinical course and complications of the disease …

Putting A Face To Cancer, Lenn Robbins

Capstones

About one month after I began my studies at the Craig Newmark Graduate School of Journalism, I was diagnosed with a rare form of cancer, Langerhans Cell Histiocytosis (LCH). Three years and three relapses later, I have my MA, I defiant will to fight this disease and the hope that by chronicling my experience I might help others. If this project helps just one person, it's been worth the ride.

https://lennrobbins.wixsite.com/facetocancer