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Dick Heinegård

Bio: Dick Heinegård is an academic researcher from Lund University. The author has contributed to research in topics: Cartilage & Proteoglycan. The author has an hindex of 90, co-authored 301 publications receiving 27074 citations. Previous affiliations of Dick Heinegård include University of Oulu & Osiris Therapeutics, Inc..


Papers
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Journal ArticleDOI
TL;DR: The results show that the Arg-Gly-Asp sequence also confers cell-binding properties on bone-specific sialoprotein, and the name "osteopontin" is proposed for this protein to better reflect the potential function of bone sIALoprotein.
Abstract: The primary structure of a bone-specific sialoprotein was deduced from cloned cDNA. One of the cDNA clones isolated from a rat osteosarcoma (ROS 17/2.8) phage lambda gt11 library had a 1473-base-pair-long insert that encoded a protein with 317 amino acid residues. This cDNA clone appears to represent the complete coding region of sialoprotein mRNA, including a putative AUG initiation codon and a signal peptide sequence. The amino acid sequence deduced from the cDNA contains several Ser-Xaa-Glu sequences, possibly representing attachment points for O-glycosidically linked oligosaccharides and one Asn-Xaa-Ser sequence representing a likely site for the N-glycosidically linked oligosaccharide. An interesting observation is the Gly-Arg-Gly-Asp-Ser sequence, which is identical to the cell-binding sequence identified in fibronectin. The presence of this sequence prompted us to investigate the cell-binding properties of sialoprotein. The ROS 17/2.8 cells attached and attained a spread morphology on surfaces coated with sialoprotein. We could demonstrate that synthetic Arg-Gly-Asp-containing peptides efficiently inhibited the attachment of cells to sialoprotein-coated substrates. The results show that the Arg-Gly-Asp sequence also confers cell-binding properties on bone-specific sialoprotein. To better reflect the potential function of bone sialoprotein--we propose the name "osteopontin" for this protein.

1,076 citations

Journal ArticleDOI
TL;DR: In this article, the interactions of three proteoglycans of the decorin family, decorin, biglycan and fibromodulin, with transforming growth factor beta (TGF-beta) were analyzed.
Abstract: We have analysed the interactions of three proteoglycans of the decorin family, decorin, biglycan and fibromodulin, with transforming growth factor beta (TGF-beta). The proteoglycan core proteins, expressed from human cDNAs as fusion proteins with Escherichia coli maltose-binding protein, each bound TGF-beta 1. They showed only negligible binding to several other growth factors. Intact decorin, biglycan and fibromodulin isolated from bovine tissues competed with the fusion proteins for the TGF-beta binding. Affinity measurements suggest a two-site binding model with Kd values ranging from 1 to 20 nM for a high-affinity binding site and 50 to 200 nM for the lower-affinity binding site. The stoichiometry indicated that the high-affinity binding site was present in one of ten proteoglycan core molecules and that each molecule contained a low-affinity binding site. Tissue-derived biglycan and decorin were less effective competitors for TGF-beta binding than fibromodulin or the non-glycosylated fusion proteins; removal of the chondroitin/dermatan sulphate chains of decorin and biglycan (fibromodulin is a keratan sulphate proteoglycan) increased the activities of decorin and biglycan, suggesting that the glycosaminoglycan chains may hinder the interaction of the core proteins with TGF-beta. The fusion proteins competed for the binding of radiolabelled TGF-beta to Mv 1 Lu cells and endothelial cells. Affinity labelling showed that the binding of TGF-beta to betaglycan and the type-I receptors in Mv 1 Lu cells and to endoglin in endothelial cells was reduced, but the binding to the type-II receptors was unaffected. TGF-beta 2 and 3 also bound to all three fusion proteins. Latent recombinant TGF-beta 1 precursor bound slightly to fibromodulin and not at all to decorin and biglycan. The results show that the three decorin-type proteoglycans each bind TGF-beta isoforms and that slight differences exist in their binding properties. They may regulate TGF-beta activities by sequestering TGF-beta into extracellular matrix.

932 citations

Journal ArticleDOI
TL;DR: The small dermatan sulphate proteoglycan of bovine tendon demonstrated a unique ability to inhibit fibrillogenesis of both type I and type II collagen from bovines tendon and cartilage respectively in an assay performed in vitro, suggesting that interactions between collagen and proteoglycans may be quite specific both for the type of proteogly can and its tissue of origin.
Abstract: The small dermatan sulphate proteoglycan of bovine tendon demonstrated a unique ability to inhibit fibrillogenesis of both type I and type II collagen from bovine tendon and cartilage respectively in an assay performed in vitro. None of the other proteoglycan populations from cartilage, tendon or aorta, even those similar in size and chemical structure, had this effect. Alkali treatment of the small proteoglycan of tendon eliminated its ability to inhibit fibrillogenesis, whereas chondroitinase digestion did not. This indicates that its interaction with collagen depends on the core protein. Fibrillogenesis of pepsin-digested collagens was affected similarly, indicating that interaction with the collagen telopeptides is not involved. The results suggest that interactions between collagen and proteoglycans may be quite specific both for the type of proteoglycan and its tissue of origin.

858 citations

Journal ArticleDOI
TL;DR: This paper attempts to give a current picture of the organization and role of the noncollagenous matrix macromolecules in cartilage and bone.—Heinegård, D.
Abstract: Over recent years a number of cartilage and bone matrix molecules have been identified and characterized. These include major constituents such as collagens and proteoglycans as well as a number of less-abundant matrix proteins. In several cases these proteins have been characterized by cloning and sequence analysis of the corresponding cDNA. Some properties of the macromolecules have been studied and an understanding of their functions in the structure, assembly, and breakdown of connective tissue matrix is emerging. It appears that some of these molecules have structural roles whereas others participate in the assembly of the tissue. In this paper we attempt to give a current picture of the organization and role of the noncollagenous matrix macromolecules in cartilage and bone.

556 citations

Journal ArticleDOI
TL;DR: Evidence is presented which suggests that the hyaluronic acid-proteoglycan interactions described by Hardingham and Muir ((1972) Biochim.

539 citations


Cited by
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Journal ArticleDOI
23 Oct 1987-Science
TL;DR: Together, the adhesion proteins and their receptors constitute a versatile recognition system providing cells with anchorage, traction for migration, and signals for polarity, position, differentiation, and possibly growth.
Abstract: Rapid progress has been made in the understanding of the molecular interactions that result in cell adhesion. Many adhesive proteins present in extracellular matrices and in the blood contain the tripeptide arginine-glycine-aspartic acid (RGD) as their cell recognition site. These proteins include fibronectin, vitronectin, osteopontin, collagens, thrombospondin, fibrinogen, and von Willebrand factor. The RGD sequences of each of the adhesive proteins are recognized by at least one member of a family of structurally related receptors, integrins, which are heterodimeric proteins with two membrane-spanning subunits. Some of these receptors bind to the RGD sequence of a single adhesion protein only, whereas others recognize groups of them. The conformation of the RGD sequence in the individual proteins may be critical to this recognition specificity. On the cytoplasmic side of the plasma membrane, the receptors connect the extracellular matrix to the cytoskeleton. More than ten proved or suspected RGD-containing adhesion-promoting proteins have already been identified, and the integrin family includes at least as many receptors recognizing these proteins. Together, the adhesion proteins and their receptors constitute a versatile recognition system providing cells with anchorage, traction for migration, and signals for polarity, position, differentiation, and possibly growth.

4,821 citations

Journal ArticleDOI
TL;DR: The histological classification of human atherosclerotic lesions found in the second part of this report led to the earlier definitions of precursor lesions, and the appearance of lesions noted in clinical imaging studies with histological lesion types and corresponding clinical syndromes was attempted.
Abstract: This report is the continuation of two earlier reports that defined human arterial intima and precursors of advanced atherosclerotic lesions in humans. This report describes the characteristic components and pathogenic mechanisms of the various advanced atherosclerotic lesions. These, with the earlier definitions of precursor lesions, led to the histological classification of human atherosclerotic lesions found in the second part of this report. The Committee on Vascular Lesions also attempted to correlate the appearance of lesions noted in clinical imaging studies with histological lesion types and corresponding clinical syndromes. In the histological classification, lesions are designated by Roman numerals, which indicate the usual sequence of lesions progression. The initial (type I) lesion contains enough atherogenic lipoprotein to elicit an increase in macrophages and formation of scattered macrophage foam cells. As in subsequent lesion types, the changes are more marked in locations of arteries with adaptive intimal thickening. (Adaptive thickenings, which are present at constant locations in everyone from birth, do not obstruct the lumen and represent adaptations to local mechanical forces). Type II lesions consist primarily of layers of macrophage foam cells and lipid-laden smooth muscle cells and include lesions grossly designated as fatty streaks. Type III is the intermediate stage between type II and type IV (atheroma, a lesion that is potentially symptom-producing). In addition to the lipid-laden cells of type II, type III lesions contain scattered collections of extracellular lipid droplets and particles that disrupt the coherence of some intimal smooth muscle cells. This extracellular lipid is the immediate precursor of the larger, confluent, and more disruptive core of extracellular lipid that characterizes type IV lesions. Beginning around the fourth decade of life, lesions that usually have a lipid core may also contain thick layers of fibrous connective tissue (type V lesion) and/or fissure, hematoma, and thrombus (type VI lesion). Some type V lesions are largely calcified (type Vb), and some consist mainly of fibrous connective tissue and little or no accumulated lipid or calcium (type Vc).

3,698 citations

Journal ArticleDOI
TL;DR: A large number of patients with progressive fibrosis have no known underlying cause of disease and the prognosis is poor, suggesting that the disease is likely to get worse as they age.
Abstract: Progressive fibrosis in the kidney, liver, lung, heart, bone marrow, and skin is both a major cause of suffering and death and an important contributor to the cost of health care. All of this is li...

2,974 citations

Journal ArticleDOI
25 Sep 1987-Science
TL;DR: Modifications to biomaterial surfaces at an atomic level will allow the programming of cell-to-substratum events, thereby diminishing infection by enhancing tissue compatibility or integration, or by directly inhibiting bacterial adhesion.
Abstract: Biomaterials are being used with increasing frequency for tissue substitution. Complex devices such as total joint replacements and the total artificial heart represent combinations of polymers and metal alloys for system and organ replacement. The major barriers to the extended use of these devices are the possibility of bacterial adhesion to biomaterials, which causes biomaterial-centered infection, and the lack of successful tissue integration or compatibility with biomaterial surfaces. Interactions of biomaterials with bacteria and tissue cells are directed not only by specific receptors and outer membrane molecules on the cell surface, but also by the atomic geometry and electronic state of the biomaterial surface. An understanding of these mechanisms is important to all fields of medicine and is derived from and relevant to studies in microbiology, biochemistry, and physics. Modifications to biomaterial surfaces at an atomic level will allow the programming of cell-to-substratum events, thereby diminishing infection by enhancing tissue compatibility or integration, or by directly inhibiting bacterial adhesion.

2,070 citations

Journal ArticleDOI
TL;DR: This research presents a novel and scalable approach to personalized medicine that addresses the underlying cause of inflammation in patients withumatoid arthritis and shows real-world implications for treatment and prognosis.
Abstract: Osteoarthritis (OA) is the most common form of arthritis and a major cause of pain and disability in older adults (1) Often OA is referred to as degenerative joint disease “(DJD)” This is a misnomer because OA is not simply a process of wear and tear but rather abnormal remodeling of joint tissues driven by a host of inflammatory mediators within the affected joint The most common risk factors for OA include age, gender, prior joint injury, obesity, genetic predisposition, and mechanical factors, including malalignment and abnormal joint shape (2, 3) Despite the multifactorial nature of OA, the pathological changes seen in osteoarthritic joints have common features that affect the entire joint structure resulting in pain, deformity and loss of function The pathologic changes seen in OA joints (Figures 1 and ​and2)2) include degradation of the articular cartilage, thickening of the subchondral bone, osteophyte formation, variable degrees of synovial inflammation, degeneration of ligaments and, in the knee, the menisci, and hypertrophy of the joint capsule There can also be changes in periarticular muscles, nerves, bursa, and local fat pads that may contribute to OA or the symptoms of OA The findings of pathological changes in all of the joint tissues are the impetus for considering OA as a disease of the joint as an organ resulting in “joint failure” In this review, we will summarize the key features of OA in the various joint tissues affected and provide an overview of the basic mechanisms currently thought to contribute to the pathological changes seen in these tissues Open in a separate window Figure 1 Sagittal inversion recovery (A–C) and coronal fast spin echo (D–F) images illustrating the magnetic resonance imaging findings of osteoarthritis (A) reactive synovitis (thick white arrow), (B) subchondral cyst formation (white arrow), (C) bone marrow edema (thin white arrows), (D) partial thickness cartilage wear (thick black arrow), (E–F) full thickness cartilage wear (thin black arrows), subchondral sclerosis (arrowhead) and marginal osteophyte formation (double arrow) Image courtesy of Drs Hollis Potter and Catherine Hayter, Hospital for Special Surgery, New York, NY

2,039 citations