Anthony M. Reginato

Reviews4 October 2005Pathogenesis of GoutHyon K. Choi, MD, DrPH, David B. Mount, MD, and Anthony M. Reginato, MD, PhDHyon K. Choi, MD, DrPHFrom Arthritis Research Centre of Canada, University of British Columbia, Vancouver, British Columbia, Canada; Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, and VA Boston Healthcare System, Boston, Massachusetts., David B. Mount, MDFrom Arthritis Research Centre of Canada, University of British Columbia, Vancouver, British Columbia, Canada; Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, and VA Boston Healthcare System, Boston, Massachusetts., and Anthony M. Reginato, MD, PhDFrom Arthritis Research Centre of Canada, University of British Columbia, Vancouver, British Columbia, Canada; Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, and VA Boston Healthcare System, Boston, Massachusetts.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-143-7-200510040-00009 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Clinical PrinciplesThe overall disease burden of gout is substantial and may be increasing.As more scientific data on the modifiable risk factors and comorbidities of gout become available, integration of these data into gout care strategies may become essential.Hyperuricemia and gout are associated with the insulin resistance syndrome and related comorbid conditions.Lifestyle modifications that are recommended for gout generally align with those for major chronic disorders (such as the insulin resistance syndrome, hypertension, and cardiovascular disorders); thus, these measures may be doubly beneficial for many patients with gout and particularly for individuals with these comorbid conditions.Effective management of risk factors for ...References1. 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Early development of the vertebrate skeleton depends on genes that pattern the distribution and proliferation of cells from cranial neural crest, sclerotomes, and lateral plate mesoderm into mesenchymal condensations at sites of future skeletal elements. Within these condensations, cells differentiate to chondrocytes or osteoblasts and form cartilages and bones under the control of various transcription factors. In most of the skeleton, organogenesis results in cartilage models of future bones; in these models cartilage is replaced by bone by the process of endochondral ossification. Lastly, through a controlled process of bone growth and remodeling the final skeleton is shaped and molded. Significant and exciting insights into all aspects of vertebrate skeletal development have been obtained through molecular and genetic studies of animal models and humans with inherited disorders of skeletal morphogenesis, organogenesis, and growth.

Angiogenesis is an essential component of skeletal development and VEGF signaling plays an important if not pivotal role in this process. Previous attempts to examine the roles of VEGF in vivo have been largely unsuccessful because deletion of even one VEGF allele leads to embryonic lethality before skeletal development is initiated. The availability of mice expressing only the VEGF120 isoform (which do survive to term) has offered an opportunity to explore the function of VEGF during embryonic skeletal development. Our study of these mice provides new in vivo evidence for multiple important roles of VEGF in both endochondral and intramembranous bone formation, as well as some insights into isoform-specific functions. There are two key differences in vascularization of developing bones between wild-type and VEGF(120/120) mice. VEGF(120/120) mice have not only a delayed recruitment of blood vessels into the perichondrium but also show delayed invasion of vessels into the primary ossification center, demonstrating a significant role of VEGF at both an early and late stage of cartilage vascularization. These findings are the basis for a two-step model of VEGF-controlled vascularization of the developing skeleton, a hypothesis that is supported by the new finding that VEGF is expressed robustly in the perichondrium and surrounding tissue of cartilage templates of future bones well before blood vessels appear in these regions. We also describe new in vivo evidence for a possible role of VEGF in chondrocyte maturation, and document that VEGF has a direct role in regulating osteoblastic activity based on in vivo evidence and organ culture experiments.