UAB Core Center for Musculoskeletal Disorders

阿拉巴马大学伯明翰分校肌肉骨骼疾病核心中心(UAB-CCMD；主任：J.McDonald，MD)的目标是使用一种协调的跨学科方法来识别和描述骨丢失和再生的关键机制以及调节这些过程的系统和局部因素，作为开发创新治疗策略的基础。主要的疾病焦点是骨质疏松症，但通过纳入具有牙周病、类风湿性关节炎和生物工程专业知识的研究人员，该计划的有效性得到了提高。UAB-CCMD拥有33名研究人员，他们在骨细胞分化和功能调控、细胞-细胞和细胞-基质相互作用以及骨细胞生长因子和激素调控方面拥有专业知识。成骨细胞/脂肪细胞分化的转录调控，细胞-细胞和细胞-基质相互作用的生长因子调控，以及相关的信号转导通路的研究将促进合成代谢疗法的发展。同样，通过研究成骨细胞功能和增殖的调节，包括通过肿瘤坏死因子/RANKL和Fas介导的通路调节，局部粘连形成的调节，以及信号转导机制的研究，将促进基于抑制成骨机制的策略。这些领域的并行发展，通过UAB-CCMD的行政核心进行协调，对于针对复杂的、多因素的骨骼疾病至关重要，并随着研究的展开迅速形成了新的合作努力。已经确定了几个新的靶点，并通过一组在该领域具有专业知识的研究人员促进了它们的翻译研究，包括分析当前治疗方法的效果，开发用于基因治疗的载体和作为实验工具。UAB-CCMD研究核心对这一动态计划的成功至关重要：1)人类骨细胞生产核心，提供人类破骨细胞和成骨细胞以及分子实验的关键试剂；2)组织形态计量学和分子分析核心，提供最先进的组织学、组织形态计量学和高灵敏度细胞和组织分子探针技术。从12篇投稿中竞争性地选出了三项P&F研究：“Smad3在成骨细胞分化中的功能”，石兴明博士；“PYK2和FAK在调节破骨细胞性骨吸收中的作用”，熊文成医学博士；以及“成骨细胞与植入材料的粘附性”，Susan Bellis，博士。UAB-CCMD有可能在骨质疏松症和相关骨病的预防和治疗方面产生快速和重大的影响。

The goal of the University of Alabama at Birmingham Core Center in Musculoskeletal Disorders (UAB-CCMD; Director: J. McDonald, MD) is to use a coordinated interdisciplinary approach to identify and characterize the key mechanisms underlying bone loss and regeneration and the systemic and local factors that regulate these processes, as a basis for the development of innovative therapeutic strategies. The primary disease focus is osteoporosis, but the effectiveness of the program is enhanced by the inclusion of investigators with expertise in periodontal disease, rheumatoid arthritis, and bioengineering. The UAB-CCMD has a research base of 33 investigators with expertise in regulation of bone cell differentiation and function; cell-cell and cell-matrix interactions; and growth factor and hormonal regulation of bone cells. Development of anabolic therapeutics will be facilitated by studies of transcriptional regulation of osteoblasts/adipocyte differentiation and the growth factor regulation of cell-cell and cell-matrix interactions, and the associated signal transduction pathways. Similarly, strategies based on the inhibition of osteopenic mechanisms will be facilitated by studies of the regulation of osteoblast function and proliferation, including regulation through the TNF/RANKL and Fas-mediated pathways, regulation of focal adhesion formation, and signal transduction mechanisms. Parallel develop of these fields, coordinated through the Administrative Core of the UAB-CCMD, is essential in targeting complex, multi-factorial bone diseases, and has led to the rapid formation of new collaborative efforts as the research unfolds. Several novel targets have been identified and their translational research is being promoted through a group of investigators with expertise in this filed, including analysis of the effects of current therapies and the development of vectors for gene therapy and as experimental tools. The UAB-CCMD Research Cores are essential to the success of this dynamic program: 1) a Human Bone Cell Production Core providing human osteoclasts and osteoblasts and key reagents for molecular experimentation; and 2) a Histomorphometry and Molecular Analysis Core providing state-of-the-art histological, histomorphometric, and highly sensitive cellular and tissue molecular probe technique. Three P&F studies have been competitively selected from 12 submissions: "The function of Smad3 in osteoblast differentiation", Xingming Shi, PhD; "Role of PYK2 and FAK in regulating osteoclastic bone resorption", Wen -Cheng Xiong, MD, PhD; and "Adhesion of osteoblasts to implant materials", Susan Bellis, PhD. The UAB-CCMD has the potential to make rapid and significant impact on the prevention and treatment of osteoporosis and related bone diseases.