[农学]代谢性骨病分子、细胞生物学.ppt

中南大学代谢内分泌研究所 中南大学代谢内分泌研究所 代谢性骨病细胞、分子生物学基础及研究方法与策略 周后德 2005. 4. 20 长沙 代谢性骨病 代谢性骨病是一类伴有钙、磷、维生素D代谢失调以及甲状旁腺功能、细胞因子与激素分泌异常的全身性骨骼病 [代谢性骨病的分类] ??? 1.骨质疏松 ??? 2.佝偻-软骨病 ??? 3.原发性甲状旁腺机能亢进症 ??? 4.原发性甲状旁腺机能减退症 ??? 5.中毒性骨病(维生素D、氟、镉、铅、磷等中毒) ??? 6.其他如粘多糖代谢异常，Marfan症，Paget症, SEDT-PA。 osteoporosis：Represents a continuum, in which multiple pathogenetic mechanisms converge to cause loss of bone mass and microarchitectural deterioration of skeletal structure. These factors, coupled with an increased risk of falls, contribute to a high incidence of fragility fractures in osteoporotic patients. Skeletal fragility can result from: (a) failure to produce a skeleton of optimal mass and strength during growth; (b) excessive bone resorption resulting in decreased bone mass and microarchitectural deterioration of the skeleton; (c) an inadequate formation response to increased resorption during bone remodeling. The bone remodeling units or bone multicellular units (BMUs) 骨组织的细胞成份 成骨谱系：间充质干细胞，骨源性始组细胞（osteoprogenitor cells）、成骨细胞（osteoblast）、骨衬细胞（bone-lining cell）、骨细胞（osteocyte） 破骨谱系：多潜能造血干细胞、破骨细胞（osteoclast） 成软骨细胞、软骨细胞、破软骨细胞 非细胞成分 组织细胞学基础 Osteoclast development and differentiation Cell-to-cell interactions in bone Bone remodeling is a dynamic process: requires coordinated cellular activities among osteoblasts, osteocytes, and osteoclasts Adherens junctions：cadherins in osteogenesis Communicating junctions：Gap junctions Connexin43 ，45， 46，the pore is different Development and maintenance of a differentiated osteoblast phenotype. activation of the ERK signaling cascade propagation of calcium wave Osteoblast/osteocyte apoptosis apoptotic osteoblasts with typical apoptotic features of condensed chromatin and/or nuclear fragmentationare seen rarely in vivo (TUNEL +) they must be juxtaposed to osteoid and to other osteoblasts because bone formation is carried out by teams of osteoblasts, but not in osteocytes they should have a cuboidal