Comparison of bone marrow extracellular matrices Myeongwoo Lee *, Indu P. Christopherson, Je¡rey M. Lehman, Cory J. Bennett, H. Tak Cheung Department of Biological Sciences, Illinois State University, Normal, IL, 61790-4120, USA Received 21 December 1998; received in revised form 27 April 1999; accepted 4 May 1999 Abstract We have compared the structure and composition of adult and fetal bovine bone marrow extracellular matrices. In contrast to fetal bone marrow, adult bone marrow has more oval fenestration and accumulation of adipocytes as well as lower protein content. These differences could be due to remodeling of bone marrow tissue as it develops. Zymogram analysis of matrix metalloproteinase (MMP) and tissue inhibitor of MMP (TIMP) activities showed that fetal, but not adult bone marrow extract contained a 96-kDa MMP and TIMP-1 and -2. These activities may contribute to the structural differences between adult and fetal bone marrow tissues. ß 1999 Elsevier Science B.V. All rights reserved. Keywords : Extracellular matrix; Bone marrow; MMP; TIMP 1. Introduction Extracellular matrix (ECM) plays an important role in many cellular processes, such as di¡erentia- tion, adhesion, and migration. Bone marrow con- tains hematopoietic and stromal cells, soluble and membrane bound growth factors, and ECM. As the primary site of hematopoiesis, this microenvironment is involved in promoting continuous proliferation, maturation, and release of blood cells [1]. During development, the location of hematopoietic activity switches from yolk sac to the fetal liver and ¢nally to bone marrow and spleen via migration of hemato- poietic progenitor cells [2]. Bone marrow stromal tissue, the major tissue of the microenvironment, develops prenatally even be- fore the maturation of hematopoietic progenitor cells, occurring in the last part of gestation and undergoes modi¢cations through development [3]. Bone marrow also changes, accumulating adipose cells by 2 weeks after birth and the yellow marrow is attained by 3^4 months [4]. Studies have also es- tablished that the pool sizes, function, and prolifer- ation of circulating blood and marrow cells are dif- ferent in those of fetal and young adults [5]. Many studies have shown that hematopoietic cells interact with ECM components and di¡erentiate into many di¡erent cell types via cell^matrix interaction [6,7]. For example, targeted destruction of K4-integ- rin gene showed global disruption of hematopoiesis, especially T- and B-cell development, suggesting the importance of cell^matrix interaction in hemato- poiesis [8]. In long-term culture systems, collagens, 0304-4165 / 99 / $ ^ see front matter ß 1999 Elsevier Science B.V. All rights reserved. PII:S0304-4165(99)00083-5 Abbreviations : EDTA, ethylenediaminetetraacetic acid; PMSF, phenylmethylsulfonyl £uoride * Corresponding author. Present address: Department of Mo- lecular Biology, Princeton University, Princeton, NJ 08544, USA ; E-mail : mlee@molbio.princeton.edu Biochimica et Biophysica Acta 1428 (1999) 300^304 www.elsevier.com/locate/bba