BAM 8 (2), 1998


Table of Contents


Hot Section: Extracellular Matrix and Muscle Development

SG Velleman, Guest Editor

Editorial        94        SG Velleman: The role of the extracellular matrix in muscle developmen

Articles         95        Dynamic expression of proteoglycans during skeletal muscle development
                                  DA Carrino    [Full text pdf 923 Kb]

                    107        Heparan sulfate proteoglycans during terminal skeletal muscle cell differentiation: possible functions
                                  and regulation of their expression
                                  E Brandan and J Larrain    [Full text pdf 320 Kb]

                    115        Skeletal muscle satellite cells: identification of heparan sulfate  proteoglycan
                                  SG Velleman, DC McFarland and CS Coy    [Full text pdf 618 Kb]

                    121        Connective tissue formation in the skeletal muscles of Transforming Growth Factor- b (TGF-b-1) null mutant mice
                                  Y Poussart, K Koishi and IS McLennan

                    129        The expression of extracellular matrix during adult skeletal muscle regeneration: how the basement membrane,
                                  interstitium and myogenic cells collaborate
                                  MD Grounds, JK McGeachie, MJ Davies, LM Sorokin and MAL Maley

                    143        Collagen crosslinking in the heart: relationship to development and function
                                  RJ McCormick and DP Thomas    [Full text pdf 258 Kb]

                    151        The alterations in the extracellular matrix of hearts from copper-deficient rats
                                  DM Medeiros and L Shiry    [Full text pdf 2.83 Mb]

                    159        Proteoglycans and meat quality - A possible role of chondroitin/dermatan sulfate proteoglycans in post mortem degradation
                                  KH Eggen, WE Ekholdt, V Høst and SO Kolset    [Full text pdf 956 Kb]

                    169        Farm animal models for cellular and molecular skeletal muscle research
                                  SK Duckett, KM Byrne, KL Hossner and MV Dodson    [Full text pdf 135 Kb]
 
 
 
 

Editorial
The Role of the Extracellular Matrix in Muscle Development

For many years, the extracellular matrix was thought to be created by connective tissue cells and surround those cells as a mere structural scaffold. The extracellular matrix was categorized as a stable inert support material that was independent from cellular activity. We now know that after the cell produces and secretes the extracellular matrix macromolecules, the cell continues to interact with the extracellular matrix and as development proceeds the molecular composition of the extracellular matrix changes in a precisely regulated fashion. Therefore, the fate of the cell in terms of its cytoskeletal organization, migration, proliferation and differentiation are related to the compositional properties of the extracellular matrix. These changes in the extracellular matrix alter the physical properties of the tissue or organ in terms of flexibility and mechanical strength. During the past decade, knowledge of the number and complexity of extracellular matrix macromolecules has significantly expanded. However, their role in tissue growth, structure, and function is somewhat an enigma. Research addressing the influence of the extracellular matrix on muscle development is in its infancy. It is now known that the extracellular matrix plays a role in skeletal muscle development, the regeneration of muscle, and in the development of cardiovascular disease. In this issue of Basic and Applied Myology, these emerging areas of research are highlighted. The papers by Carrino, Poussart et al., and Brandan and Larrain discuss skeletal muscle and connective tissue development. The genetic regulation of skeletal muscle development and its surrounding connective tissue is not well understood. These papers explore the dynamic expression of proteoglycans, the role of heparan sulfate proteoglycans in terminal skeletal muscle differentiation, and the potential influence of a key growth factor on connective tissue formation. In addition to the extracellular matrix playing a critical role in the formation of skeletal muscle, Grounds et al. describe changes in the expression extracellular matrix components with the progression of skeletal muscle regeneration in vivo. During the repair and regeneration of skeletal muscle, myogenic satellite cells are activated. Velleman et al. report the presence of a satellite cell produced heparan sulfate proteoglycan. Despite a decrease in mortality from heart disease since the 1960's, cardiovascular disease remains a primary cause of death. Many complex factors lead to the onset of cardiovascular disease. It is now known that the extracellular matrix undergoes significant changes during the progression of various cardiac pathologies which may contribute to increased stiffness and enlargement of the heart. Papers by McCormick and Thomas, and Medeiros and Shiry discuss extracellular matrix changes that occur in the myocardium. The muscle foods industry comprises a significant part of the agricultural economy. Tenderness is an important factor by which consumers judge muscle food quality and is influenced by connective tissue. In the paper by Eggen et al. a possible role of chondroitin/dermatan sulfate proteoglycans in post mortem meat tenderness is discussed. It is impossible in an issue of this nature to report on all aspects of muscle extracellular matrix biology. Emerging areas of significant biological impact have been addressed by leaders in their respective fields. We hope, this issue provides a strong survey of these areas and stimulates further scientific investigation.

Sandra G. Velleman, Ph.D. The Ohio State University/Ohio Agricultural Research and Development Center Wooster, OH

Dynamic Expression of Proteoglycans during Skeletal Muscle Development
David A. Carrino
Skeletal Research Center, Department of Biology, Case Western Reserve University, Cleveland, Ohio, USA

Proteoglycans are glycoconjugates composed of a core protein and covalently attached glycosaminoglycans. Skeletal muscle produces a number of different types of proteoglycans, and, importantly, the types of proteoglycans made by skeletal muscle vary during muscle development. At early stages of muscle development, large chondroitin sulfate proteoglycans of the PG-M/versican type are produced both in culture and in vivo. Localization both by autoradiography of radiolabeled material and by immunohistochemistry indicates that the chondroitin sulfate proteoglycans are deposited in a pericellular region around the muscle cells. Although biosynthesis of these molecules is not detected in mature skeletal muscle, their synthesis is re-initiated during regeneration, which suggests a requirement for these molecules in some early aspect of muscle development. At later stages of muscle development, small dermatan sulfate proteoglycans are synthesized. One of the major types of dermatan sulfate proteoglycans in skeletal muscle is decorin, which can bind to collagen and affect fibril formation. Decorin is initially localized in the fibrous connective tissue areas of skeletal muscle, but eventually, at later stages of muscle development, is also found in proximity to the myotubes. Heparan sulfate proteoglycans are also present in skeletal muscle, and among these are molecules of the syndecan, glypican, and perlecan types. Heparan sulfate proteoglycans are significant because of their involvement in signal transduction of growth factors such as fibroblast growth factor. Evidence indicates that heparan sulfate proteoglycans play a role in the stimulation of myoblast proliferation by fibroblast growth factor. The exact roles played by other proteoglycans in muscle development are unclear at present. However, proteoglycans have the ability to affect cell adhesion and migration, processes which are important in muscle development. Because of this, it is likely that the changing patterns of proteoglycan biosynthesis during muscle development are part of and, indeed, influence the orchestrated cellular interactions which are essential for proper muscle formation.
Key words: proteoglycan, extracellular matrix, muscle development, chondroitin sulfate, heparan sulfate, dermatan sulfate.
Basic Appl. Myol. 8 (2): 95-106, 1998

Skeletal Research Center, Department of Biology, Case Western Reserve University, Cleveland, Ohio, USA, 44106-7080.

Heparan Sulfate Proteoglycans during Terminal Skeletal Muscle Cell Differentiation: Possible Functions and Regulation of their Expression
Enrique Brandan and Juan Larrain
Department of Cell and Molecular Biology, Faculty of Biological Sciences, Catholic University of Chile, Santiago, Chile

Heparan sulfate proteoglycans are key molecules found associated with the cell surface and extracellular matrix (ECM). These macromolecules seem to be essential to achieve terminal skeletal muscle differentiation. In this review, we present data about the types of heparan sulfate proteoglycans present in skeletal muscle cells, how their expression changes during differentiation and we propose some mechanisms that might be controlling and/or affecting their expression. Finally, we discuss some possible functions for these heparan sulfate proteoglycans during skeletal muscle differentiation.
Key words: myogenesis, proteoglycans, growth factors, cell differentiation, heparan.
Basic Appl. Myol. 8 (2): 107-113, 1998

E. Brandan, Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, P. Universidad Católica de Chile, Casilla 114-D, Santiago, Chile, fax 56 2 686 2717, Email ebrandan@genes.bio.puc.cl@.

Skeletal Muscle Satellite Cells: Identification of a Heparan Sulfate Proteoglycan
Sandra G. Velleman, Douglas C. McFarland (1) and Cynthia S. Coy
The Ohio State University/Ohio Agricultural Research and Development Center, Department of Animal Sciences, Wooster and (1) South Dakota State University, Department of Animal and Range Sciences, Brookings

Skeletal muscle fibers are surrounded by an extracellular matrix. The extracellular matrix is composed of glycoproteins, collagen, and proteoglycans. Proteoglycans have been suggested by different reports to play an important functional role in tissue differentiation. However, an understanding of how proteoglycans modulate skeletal muscle differentiation and the activation of myogenic satellite cells is largely unknown. In the present study, chicken pectoral muscle satellite cells were screened for the synthesis and localization of a heparan sulfate proteoglycan during satellite cell proliferation and differentiation. A heparan sulfate proteoglycan was detected during the proliferative phase of cell growth. After the induction of fusion, the heparan sulfate proteoglycan had both an intracellular and extracellular distribution. Based on the reported function of heparan sulfate proteoglycans as a modulator of basic fibroblast growth factor activity, it is possible that a satellite cell produced heparan sulfate proteoglycan may interact with basic fibroblast growth factor and be a key component in the satellite cell response to basic fibroblast growth factor.
Key words: muscle, satellite cell, heparan sulfate, proteoglycans.
Basic Appl. Myol. 8 (2): 115-120, 1998

Sandra G. Velleman, The Ohio State University/OARDC, Department of Animal Sciences, Rm. 213 Gerlaugh Hall, 1680 Madison Ave., Wooster, OH 44691, tel. 330 263 3905, fax 330 263 3949, E-mail velleman.1@osu.edu.

Connective Tissue Formation in the Skeletal Muscles of Transforming Growth Factor-b1 (TGF-b1) Null Mutant Mice
Yves Poussart (1, 2), Kyoko Koishi (1) and Ian S. McLennan (1)
(1) Department of Anatomy and Structural Biology, University of Otago, Dun-edin,New Zealand and (2) Departement de Biologie, Universite de Moncton, Nouveau-Brunswick, Canada

Transforming growth factor-b 1 (TGF-b1) has been postulated to control the division of muscle primordia into distinct connective tissue and myogenic zones, as well as promoting the differentiation of the epimysium and perimysium. TGF-b1 null-mutant mice, which have a disrupted TGF-b1 gene, were used to test these hypotheses. The leg muscles from newborn TGF-b1 null-mutant and wild-type pups were serially sectioned from the knee to the ankle and selected sections stained using either immunohistochemistry with antibodies to collagen I, collagen IV, fast myosin and slow myosin or histologically with haematoxylin and eosin. The locations and sizes of the epimysium and perimysium were normal in the TGF-b1 null-mutant neonates, as were the amounts of collagen immunoreactivities in the various connective tissues. Muscle fibres were not detected in the major connective tissues of the muscles of the null mutant pups, indicating that the division of the muscle primordia into myogenic and connective tissue zones is normal in the absence of local production of TGF-b1. These observations suggest that TGF-b1 is not a major regulator of skeletal muscle connective tissue formation.
Key words: epimysium, perimysium, myotube, differentiation, pattern.
Basic Appl. Myol. 8 (2): 121-127, 1998

Ian S McLennan, Department of Anatomy and Structural Biology, University of Otago, PO Box 913, Dunedin, New Zealand, phone 64 3 479 7364, fax 64 3 479 7254, Email ian.mclennan@stonebow.otago.ac.nz.

The Expression of Extracellular Matrix During Adult Skeletal Muscle Regeneration: How the Basement Membrane, Interstitium and Myogenic Cells Collaborate
Miranda D. Grounds, John K. McGeachie, Marilyn J. Davies, Lydia M. Sorokin (1) and Moira A.L. Maley
Department of Anatomy and Human Biology, The University of Western Australia, Australia and (1) Connective Tissue Laboratory, Institute for Experimental Medicine, University of Erlangen, Germany

To determine whether differences in the expression of extracellular matrix (ECM) components correlate with the progression of skeletal muscle regeneration in vivo, the location and intensity of expression of basement membrane components (laminin a1, a2, a5 chains and collagen IV), matrix proteins upregulated during inflammation (fibronectin and tenascin-C), and cell adhesion molecules (VCAM-1 and a4 b1 integrin) were examined by immunofluorescent tissue staining in two models of muscle regeneration in mice. Crush injury results in major disruption of the basement membranes of myofibres and an early inflammatory response, whereas in whole muscle grafts the tissue architecture is largely preserved and there is a delayed inflammatory response. The patterns of ECM expression were similar in both models and corresponded closely with key cellular events. The only difference was the loss of basement membrane component immunoreactivity in necrotic myofibres in the centre of the crush injured muscles compared with sustained immunoreactivity in whole muscle grafts. There were no differences in the relative expression of ECM components between crushed muscles from SJL/J and BALB/c mice, which have a different efficiency of muscle regeneration following crush injury in vivo.
Key words: skeletal muscle, regeneration, injury, mice, extracellular matrix.
Basic Appl. Myol. 8 (2): 129-141, 1998

Miranda M. Grounds, Department of Anatomy and Human Biology, The University of Western Australia, Nedlands, Western Australia 6907.

Collagen Crosslinking in the Heart: Relationship to Development and Function
Richard J. McCormick and D. Paul Thomas
Department of Animal Science and Human Energy Research Laboratory, University of Wyoming, Laramie

The hydroxypyridinium (HP) crosslink is the predominant non-reducible collagen crosslink in heart. HP concentration in left ventricle (LV) increases progressively throughout life, and this increase is thought to reflect the slower turnover of collagenous proteins seen with aging, allowing mature extracellular matrix (ECM) collagen to crosslink more heavily. There are also species differences with higher levels of crosslinking found in the hearts of larger mammals including humans, compared to smaller mammals such as the rat. Marked deviations from normal in the concentration of this crosslink are implicated in a variety of left ventricular hypertrophies and altered ventricular function. Interestingly these deviations may be bi-directional in nature, ranging from an apparent lack of the crosslink in a mouse cardiomyopathy model, to a doubling in HP concentration in viable myocardium post-infarction. This review outlines the major pathway involved in the formation of myocardial collagen crosslinks. Possible mechanisms by which rate of crosslink formation and deposition are regulated will be discussed, and functional implications of altered crosslinking patterns addressed.
Key words: collagen, crosslinking, heart, myocardium, decorin.
Basic Appl. Myol. 8 (2): 143-150, 1998

Richard J. McCormick, Department of Animal Science, University of Wyoming, Laramie, WY 82071, phone 307 766 6209, fax 307 766 2355, Email: RMCCRMCK@UWYO.edu.

The Alterations in the Extracellular Matrix of Hearts from Copper-Deficient Rats
Denis M. Medeiros and Laura Shiry
Department of Human Nutrition and Food Management, Ohio Agricultural and Research Development Center, The Ohio State University, Columbus

Morphological and biochemical aspects of the copper-deficient heart model are briefly reviewed in terms of intracellular and extracellular changes. The extracellular aspects of hearts from copper-deficient rats demonstrate fibrosis and thickened and fragmented basal laminae. In addition, heart valves from copper-deficient rats have altered morphological character and are thickened compared to valves from copper-adequate rats. The ultrastructural observations pertaining to the altered basal laminae are pursued in this study in terms of immunohistological staining against specific proteins that compose the structure. Specifically, we fed copper-adequate and deficient diets to rats for 5 weeks and processed the hearts for light microscopy and immunohistochemistry. From such observations it could be inferred that the hearts from copper-deficient rats had markedly increased staining for Type IV collagen and fibronectin, whereas the reverse for laminin was observed in that little staining was detected in the copper-deficient myocytes. Furthermore, there was increased binding of the antibody against the laminin receptor in the copper-deficient rats. The implications of the compromised basal laminae in the heart are discussed.
Key words: copper, basal laminae, Type IV collagen, laminin, fibronectin, integrin.
Basic Appl. Myol. 8 (2): 151-158, 1998

Denis M. Medeiros, Department of Human Nutrition and Food Management, Ohio Agricultural and Research Development Center, 357 Campbell Hall, 1787 Neil Avenue, The Ohio State University, Columbus, OH 43210-1295, phone 614 292 5575, fax 614 292 7536, Email Medeiros.2@osu.edu.

Proteoglycans and Meat Quality - A Possible Role of Chondroitin/Dermatan Sulfate Proteoglycans in Post Mortem Degradation
Kirsten H. Eggen, Wenche E. Ekholdt, Vibeke Host and Svein O. Kolset (1)
MATFORSK - Norwegian Food Research Institute, <@197>s and (1) Institute for Nutrition Research, University of Oslo, Oslo, Norway

The knowledge of components involved in post mortem degradation of striated muscle is of great importance for the meat industry in order to provide tender meat for the consumer. To address this problem the present study has focused on proteoglycans. Proteoglycans were extracted from meat (M. semimembranosus) stored for 0, 7, 14 and 21 days post mortem by use of denaturing agents. The content of glycosaminoglycans (GAGs) in the extracts showed a reduction during post mortem storage of meat whereas the protein content showed a small increase. The reduction in GAGs could be explained by degradation of proteoglycans of high as well as low molecular mass judged by gel filtration, ion exchange chromatography and electrophoresis. Among the low molecular size PG, decorin was identified by use of antibodies and Western blotting. This collagen interacting molecule was shown to be degraded during post mortem storage. Furthermore it was shown by ion-exchange chromatography and electrophoresis that the degradation of decorin involved both the peptide core and the GAG side chains. Judged by immunohistochemistry the proteoglycans involved in degradation showed a widespread distribution in the extracellular matrix.
Key words: chondroitin/dermatan sulfate, decorin, aggrecan-like PG, meat texture, tenderness.
Basic Appl. Myol. 8 (2): 159-168, 1998

Kirsten H. Eggen, MATFORSK - Norwegian Food Research Institute, Osloveien 1, N-1430 Ås, Norway, phone +4764970221, fax +4764970333, Email kirsten.eggen@matforsk.no.

Farm Animal Models for Cellular and Molecular Skeletal Muscle Research
Susan K. Duckett, Katherine M. Byrne (1), Kim L. Hossner (2) and Michael V. Dodson (1)
University of Idaho, Moscow, (1) Washington State University, Pullman and (2) Colorado State University, Ft Collins

The idea of using farm animals to serve mankind far exceeds their use as a source of meat. Farm animals make excellent models for investigating tissue growth, producing biological materials for human use, and developing surgical protocols, artificial organ-replacement devices and medication doses. Domesticated sheep have recently been identified that display selective muscle hypertrophy under the influence of a single gene. These animals, along with certain breeds of cattle that display double muscling as a result of hyperplasia, represent new domestic animal models applicable for cellular and molecular skeletal muscle research. Combined with recent advances in cloning and gene transfer, these animal models provide powerful tools for the investigation of cellular and molecular mechanisms that regulate muscle development.
Key words: muscle, hypertrophy, hyperplasia, cloning, transgenics.
Basic Appl. Myol. 8 (2): 169-173, 1998

Dr Susan K. Duckett, University of Idaho, 216 Ag Science Bldg, Moscow, ID 83844-2330, phone 208 885 7390, fax 208 885 6420, Email sduckett@uidaho.edu.