Cell-cell communication in the osteoblast/osteocyte lineage

被引:192
作者
Civitelli, Roberto [1 ,2 ]
机构
[1] Washington Univ, Dept Internal Med, Div Bone & Mineral Dis, St Louis, MO 63110 USA
[2] Washington Univ, Dept Cell Biol & Physiol, Div Bone & Mineral Dis, St Louis, MO 63110 USA
关键词
connexin; bone; osteoblast; osteocyte; cell-cell communication; mouse genetics; gap junctions;
D O I
10.1016/j.abb.2008.04.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Skeletal development (bone modeling) and its maintenance in post-natal life in response to local and systemic stimuli (bone remodeling) require coordinated activity among osteoblasts (bone forming cells), osteocytes (cells embedded in bone) and osteoclasts (bone resorbing cells), in order to meet the needs of structural integrity, mechanical competence and maintenance of mineral homeostasis. One mechanism of cell-cell interaction is via direct cell-cell communication via gap junctions. These are transmembrane channels that allow continuity of cytoplasms between communicating cells. The biologic importance of connexin43 (Cx43), the most abundant gap junction protein in the skeleton is demonstrated by the skeletal malformations present in oculodentodigital dysplasia (ODDD), a disease linked to Cx43 gene (GJA1) mutations, and by the low bone mass and osteoblast dysfunction in Gja1 ablated mice. The presence of Cx43 is required for osteoblast differentiation and function, and by forming either gap junctions or "hemichannels" Cx43 allows participation of cell networks to responses to extracellular stimuli, via propagation of specific signals converging upon connexin sensitive transcriptional units. Hence, Cx43 is involved in skeletal responsiveness to anabolic signals, as those provided by parathyroid hormone and physical load, the latter function probably involving osteocyte-osteoblast communication. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:188 / 192
页数:5
相关论文
共 60 条
[1]   Development of mice with osteoblast-specific connexin43 gene deletion [J].
Castro, CHM ;
Stains, JP ;
Sheikh, S ;
Szejnfeld, VL ;
Willecke, K ;
Theis, M ;
Civitelli, R .
CELL COMMUNICATION AND ADHESION, 2003, 10 (4-6) :445-450
[2]   Expression of functional gap junctions and regulation by fluid flow in osteocyte-like MLO-Y4 cells [J].
Cheng, BX ;
Zhao, SJ ;
Luo, J ;
Sprague, E ;
Bonewald, LF ;
Jiang, JX .
JOURNAL OF BONE AND MINERAL RESEARCH, 2001, 16 (02) :249-259
[3]   Mechanical strain opens connexin 43 hemichannels in osteocytes: A novel mechanism for the release of prostaglandin [J].
Cherian, PP ;
Siller-Jackson, AJ ;
Gu, SM ;
Wang, X ;
Bonewald, LF ;
Sprague, E ;
Jiang, JX .
MOLECULAR BIOLOGY OF THE CELL, 2005, 16 (07) :3100-3106
[4]   Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43 [J].
Chung, Dong Jin ;
Castro, Charlles H. M. ;
Watkins, Marcus ;
Stains, Joseph P. ;
Chung, Min Young ;
Szejnfeld, Vera Lucia ;
Willecke, Klaus ;
Theis, Martin ;
Civitelli, Roberto .
JOURNAL OF CELL SCIENCE, 2006, 119 (20) :4187-4198
[5]   CONNEXIN43 MEDIATES DIRECT INTERCELLULAR COMMUNICATION IN HUMAN OSTEOBLASTIC CELL NETWORKS [J].
CIVITELLI, R ;
BEYER, EC ;
WARLOW, PM ;
ROBERTSON, AJ ;
GEIST, ST ;
STEINBERG, TH .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 91 (05) :1888-1896
[6]   The conditional connexin43G138R mouse mutant represents a new model of hereditary oculodentodigital dysplasia in humans [J].
Dobrowolski, Radoslaw ;
Sasse, Philipp ;
Schrickel, Jan W. ;
Watkins, Marcus ;
Kim, Jung-Sun ;
Rackauskas, Mindaugas ;
Troatz, Clemens ;
Ghanem, Alexander ;
Tiemann, Klaus ;
Degen, Joachim ;
Bukauskas, Feliksas F. ;
Civitelli, Roberto ;
Lewalter, Thorsten ;
Fleischmann, Bernd K. ;
Willecke, Klaus .
HUMAN MOLECULAR GENETICS, 2008, 17 (04) :539-554
[7]  
DONAHUE HJ, 1995, J BONE MINER RES, V10, P881
[8]   Gap junctions and biophysical regulation of bone cell differentiation [J].
Donahue, HJ .
BONE, 2000, 26 (05) :417-422
[9]   MORPHOLOGICAL EVIDENCE OF GAP-JUNCTIONS BETWEEN BONE-CELLS [J].
DOTY, SB .
CALCIFIED TISSUE INTERNATIONAL, 1981, 33 (05) :509-512
[10]   New roles for connexons [J].
Ebihara, L .
NEWS IN PHYSIOLOGICAL SCIENCES, 2003, 18 :100-103