Hepatocyte growth factor and alternative splice variants - expression, regulation and implications in osteogenesis and bone health and repair.
Hepatocyte growth factor and alternative splice variants - expression, regulation and implications in osteogenesis and bone health and repair.
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DOI：
10.1517/14728222.2016.1162293
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发表时间：
2016-09
影响因子：
5.8
通讯作者：
Howard GA
中科院分区：
文献类型：
--
作者：
Frisch RN;Curtis KM;Aenlle KK;Howard GA
骨髓源性间充质干细胞（MSCs）可以分化为多种细胞类型，包括成骨细胞、软骨细胞和脂肪细胞。这些多能细胞分泌肝细胞生长因子（HGF），调节细胞生长、存活、运动、迁移、有丝分裂，对组织发育/再生很重要。HGF有四种剪接变体，NK1、NK2、NK3和NK4，它们对HGF受体cMET具有不同的功能和亲和力。HGF促进MSCs向成骨细胞分化，在骨骼发育、健康和修复中发挥作用。本文将重点介绍HGF在骨生成、骨修复和骨健康中的作用，包括HGF在体内的结构和功能作用。每年大约有620万美国人经历骨折，其中5-10%为畸形或不愈合骨折。HGF在诱导MSCs体外成骨分化中很重要，目前正在研究其在体内骨修复中的作用。由于全身HGF的高周转率，人们正在研究非经典的HGF治疗模式，包括裸质粒HGF输送和HGF剪接变体（NK1和NK2）的使用，以寻找安全有效的治疗骨疾病，如畸形或不愈合骨折。
Bone marrow-derived mesenchymal stem cells (MSCs) can differentiate into multiple cell types, including osteoblasts, chondrocytes, and adipocytes. These pluripotent cells secrete hepatocyte growth factor (HGF), which regulates cell growth, survival, motility, migration, mitogenesis and is important for tissue development/regeneration. HGF has four splice variants, NK1, NK2, NK3, and NK4 which have varying functions and affinities for the HGF receptor, cMET. HGF promotes osteoblastic differentiation of MSCs into bone forming cells, playing a role in bone development, health and repair. This review will focus on the effects of HGF in osteogenesis, bone repair and bone health, including structural and functional insights into the role of HGF in the body. Approximately 6.2 million Americans experience a fracture annually, with 5–10% being mal- or non-union fractures. HGF is important in priming MSCs for osteogenic differentiation in vitro and is currently being studied to assess its role during bone repair in vivo. Due to the high turnover rate of systemic HGF, non-classic modes of HGF-treatment, including naked-plasmid HGF delivery and the use of HGF splice variants (NK1 & NK2) are being studied to find safe and efficacious treatments for bone disorders, such as mal- or non-union fractures.
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DOI：
10.1016/s0165-3806(97)00108-9
发表时间：
1997-09-20
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Achim, CL;Katyal, S;Michalopoulos, GK
通讯作者：
Michalopoulos, GK
影响因子：
4.1
作者：
Chen, Ketian;Perez-Stable, Carlos;Howard, Guy A.
通讯作者：
Howard, Guy A.
DOI：
10.1007/bf03160014
发表时间：
1992-12-01
期刊：
MOLECULAR AND CHEMICAL NEUROPATHOLOGY
影响因子：
--
作者：
HARTMANN, HA;SUN, DY
通讯作者：
SUN, DY
影响因子：
4.8
作者：
Cioce, V;Csaky, KG;Rubin, JS
通讯作者：
Rubin, JS
影响因子：
4.1
作者：
Grumbles, RM;Howell, DS;Roos, BA
通讯作者：
Roos, BA