西湖名师论坛第六期 | 曹旭:陆生脊椎动物骨骼进化与其相关的骨骼疾病

来源:WIAS 发布时间:2018-05-02 作者: 阅读数:894次


题目:Skeletal Evolution of Terrestrial Vertebrates and its Related Bone Diseases

陆生脊椎动物骨骼进化与其相关的骨骼疾病

时间:2018年5月7日(周一)   下午1:30- 2:30

地点:西湖大学云栖校区5号楼一楼学术报告厅

本期主讲嘉宾:Prof. Xu Cao,Department of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD

美国约翰霍普金斯大学骨科讲席教授


讲座摘要:

不同于水生脊椎动物,陆生脊椎动物为了承受身体的重量以及储蓄钙和其他矿物质,他们逐渐进化发育出骨骼。在适应陆生的过程中,陆生动物发育出破骨细胞和甲状旁腺激素,从水生脊椎动物的实体骨进化为充满骨髓细胞的皮质骨。

于是,陆生动物的骨骼,譬如人类的骨骼,不断地处于不断被形成和被吸收的重塑过程之中。重建过程能使骨骼结构保持完整,修复组织损伤,保持钙磷代谢的稳态。这种骨重建是通过成骨细胞和破骨细胞的精确协调来完成的。骨吸收和骨形成并不是沿着骨表面随机发生的,相反,它们发生在特定的解剖部位,并遵循一个明确的事件序列,骨重塑周期,以维持骨骼的动态平衡。破骨细胞骨吸收过程中释出放的转化生长因子b引导间充质干细胞在骨吸收部位迁移,从而形成新骨。此外,破骨细胞从骨基质中释放出IGF-1,破骨细胞分泌PDGF-BB,促进骨形成和血管生成。

然而,如果陆地脊椎动物在适应过程中的骨形成和骨吸收的耦合不平衡或耦合,就会产生许多不同的骨疾病,如骨质疏松症和骨关节炎(OA)。骨关节炎是最常见的退行性关节疾病,没有任何治疗方法。我们的研究发现,在软骨下骨内的转化生长因子b异常激活会导致骨关节炎发生时骨重塑异常和骨髓Osterid胰岛的形成。软骨下骨力学性能的改善可减轻骨关节炎(OA)关节软骨退变。

 

邀请人:基础医学研究所PI 周峰泉、郑厚峰

主持人:周峰泉教授

 

Abstract:

Terrestrial vertebrates evolutionally developed their skeletons to bear their body weights for locomotion and storage for calcium and other minerals from aquatic vertebrates where there their skeletons do not bear body weights in the ocean and the minerals are readily available. In adaptation of terrestrial life, land animals developed osteoclasts and parathyroid hormone to change solid bones of aquatic vertebrates to cortical bones with cavity filled with bone marrow cells.

As a result, their bones such as human is constantly under remodeling that is continuously being formed and resorbed. The remodeling process is necessary to maintain the structural integrity of the skeleton and allows the repair of tissue damage and homeostasis of calcium and phosphorous metabolism. This bone remodeling is accomplished by precise coordination of osteoblasts and osteoclasts. Bone resorption and formation do not occur randomly along the bone surface. Rather, they occur at specific anatomical sites and follow a well-defined sequence of events, the bone remodeling cycle, to maintain bone homeostasis. TGFβ released during osteoclast bone resorption directs the migration of mesenchymal stem cells (MSCs) to form the new bone at the resorption site. In addition, IGF-1 liberated from bone matrix by osteoclasts and PDGF-BB secreted by osteoclasts in coupling bone formation and angiogenesis.

However, if coupling of bone formation and resorption developed during adaptation for terrestrial vertebrates is not balanced or coupled, it generates many different bone diseases such as osteoporosis and osteoarthritis (OA).  OA is the most common degenerative joint disease and no disease-modifying therapy for OA. We found that aberrant activation TGFβ in the subchondral bone leads to abnormal bone remodeling and the formation of marrow osteroid islets at onset of OA. Improving mechanical properties of subchondral bone attenuates articular cartilage degeneration of OA.  


      报名链接:http://www.wias.org.cn/index.php?a=detailt&type=6