Macromolecular Aggregation States in Relation to Mineralization: The Collagen-Hydroxyapatite System as Studied in Vitro

Glimcher, Melvin J.; Hodge, Alan J.; Schmitt, Francis O.

doi:10.1073/pnas.43.10.860

Cited by 157 publications

(57 citation statements)

References 16 publications

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“…The process requires the synthesis and assembly of extracellular components (e.g. collagen, GAGs, fibronectin) that form the matrix into which mineral is deposited [23][24][25][26][27]. In consequence, bone growth and differentiation are associated with complex patterns of ECM accumulation.…”

Section: Discussionmentioning

confidence: 99%

**Apert's syndrome: differential in vitro production of matrix macromolecules and its regulation by interleukins**

Bodo¹,

Carinci

Baroni

et al. 1997

Eur J Clin Investigation

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Abstract. During embryonic development, variations in the composition of the extracellular matrix (ECM) macromolecules influence bone tissue differentiation. We present novel findings on the in vitro phenotypic expression of periosteal fibroblasts obtained from patients affected by Apert's syndrome, a rare craniofacial malformation, and the effects that interleukins (ILs) induce on the phenotype. Apert fibroblasts synthesized greater quantities of glycosaminoglycans (GAGs) and intracellular type I collagen, and also produced more type III collagen and fibronectin. The amount of hyaluronic acid (HA) secreted by Apert fibroblasts was much higher than that secreted by normal fibroblasts, but, as the absolute values of heparan sulphate (HS), chondroitin sulphate (CS) and dermatan sulphate (DS) also rose in Apert media, the HA-sulphated GAG ratio was similar in the media obtained from both populations. Both ILs triggered elevations of HA in normal cells, although relative percentage secretion remained unaltered, but significantly reduced HA secretion by Apert cells. IL-1 significantly increased CS in normal and Apert media, whereas IL-6 enhanced HS and DS in media of both populations. HA-sulphated GAG ratio decreased in Apert media after IL treatment. Both ILs boosted fibronectin production by Apert fibroblasts, whereas IL-1 increased type III but not type I collagen. Taken together, these data demonstrate that the synthesis and secretion of ECM macromolecules are markedly altered in Apert fibroblasts. The fact that treatment with ILs further modifies the Apert phenotype suggests that ILs may be implicated in the pathophysiology of the malformations during skull morphogenesis.

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Section: Discussionmentioning

confidence: 99%

**Apert's syndrome: differential in vitro production of matrix macromolecules and its regulation by interleukins**

Bodo¹,

Carinci

Baroni

et al. 1997

Eur J Clin Investigation

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“…Nevertheless, it raises the possibility that bone mineralization may also be explained by the absence of inhibitors of mineralization in the bone matrix. Work from Glimcher and collaborators >40 years ago showed that calcium and phosphate can precipitate passively on collagen, and this was viewed as an indication that collagen molecules are the initiators of mineralization (Glimcher et al 1957). A similar ability was later shown for elastin and fibronectin (Seligman et al 1975;Daculsi et al 1999).…”

Section: Bone Mineralizationmentioning

confidence: 93%

The genetic transformation of bone biology

Karsenty

1999

Genes & Development

281

179

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The skeleton, like every organ, has specific developmental and functional characteristics that define its identity in biologic and pathologic terms. Skeleton is composed of multiple elements of various shapes and origins spread throughout the body. Most of these skeletal elements are formed by two different tissues, cartilage and bone, and each of these two tissues has its own specific cell types: the chondrocyte in cartilage, and the osteoblast and osteoclast in bone. Finally, each of these cell types has its own differentiation pathway, physiological functions, and therefore pathological conditions. The complexity of this organ in terms of developmental biology, physiology, and pathology, along with the multitude of important conceptual advances in our understanding of skeletal biology, are such that it has become impossible to present in a short review an up-to-date summary of both cartilage and bone biology. Thus, this review will concentrate only on bone biology beyond embryonic patterning. The entire bone field is dominated by the impact of degenerative diseases, such as osteoporosis. This mere fact does influence the research in bone biology and will influence the topics presented in this review. It is no surprise that, like for most other organogenesis processes, human and mouse genetic studies have been a major driving force in redefining bone biology. Genetic studies have opened new areas of research, elucidated at the molecular level some known phenomena, and sometimes challenged untested textbook assumptions, thus transforming the field profoundly.In mammals, bone development is a late embryonic event as it is the last event of skeleton development. Once the mesenchymal condensations prefiguring each future skeletal element have formed, between 10.5 and 12.5 days postcoitum (dpc) in mouse, they can evolve along two different paths. In some skeletal elements, prefiguring part of the skull and the clavicles, the cells of the mesenchymal condensations differentiate directly into osteoblasts that appear at 15.5 dpc of mouse development (Hall and Miyake 1992;Huang et al. 1997). This process is called intramembranous ossification. For the rest of the future skeleton, cells of the mesenchymal condensations differentiate into chondrocytes forming the "cartilage anlagen" of the future bones. In the periphery of the anlage, cells from the perichondrium differentiate into osteoblasts, while the periphery of the anlage become hypertrophic. Eventually, the matrix surrounding these hypertrophic chondrocytes calcifies and blood vessel invasion of the calcified cartilage brings in osteoblasts ∼14.5-15.5 dpc (Horton 1993;Erlebacher et al. 1995). Once a bone matrix is deposited the bone marrow forms and the first osteoclasts appear (Hofstetter et al. 1995). Thus, sequential appearance of a cartilage anlage, calcified cartilage, and then bona fide bone characterizes the endochondral ossification. Regardless of the mode of ossification, osteoblast differentiation precedes osteoclast differentiation.One peculiar characte...

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“…However, various evidences have suggested that interaction between Ca-P compounds and macromolecules might be involeved in bone development. The interaction has been suggested between HA crystals and collagens (Glimcher et al 1957) or noncollagenous proteins in bone and teeth such as osteocalcin (Hauschka et al 1975), osteonectin (Termine et al 1981), bone phosphoproteins including osteopontin (Glimcher et al 1979) and sialoproteins and proteoglycans (Fisher et al 1987). Eanes et al (1973) have suggested that ACP could be the nucleating locus for bone nodules which were described as the developmental units of bone (Bernard and Pease 1969), because of general similarity in appearance between bone nodules and clusters of synthetic HA formed by conversion of ACP.…”

Section: Light Microscopic Findingsmentioning

confidence: 99%

Bone Formation on Synthetic Precursors of Hydroxyapatite.

Сузукі

Nakamura

Miyasaka

et al. 1991

Tohoku J. Exp. Med.

265

312

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The aim of this study was to investigate the reaction of skeletal tissue to various synthetic calcium phosphate (Ca-P) compounds in vivo. Five synthetic Ca-P compounds were implanted into the subperiosteal area of the calvaria of 7-week-old BALB/c mice for one to 15 weeks. Synthetic compounds were dicalcium phosphate (DCP), octacalcium phosphate (OCP), amorphous calcium phosphate (ACP), Ca-deficient hydroxyapatile and hydroxyapatile (HA). Implanted DCP, OCP and ACP were found to be converted to apatitic phase by x-ray microdiffraction analysis using undecalcified specimens. Structure of bone was found out on all of Ca-P compounds eventually at late stage under the light microscope, but the rate of bone formation calculated from a number of experiments varied on respective synthetic Ca-P compound. It was high as 80% for DCP, OCP and ACP, but was low as 5.6% for Ca-deficient HA, and no reaction was found for HA at the stage of 3 weeks. Fine filaments and granular materials in the newly formed bone matrix were detected at 7 days around the remnants of OCP particles which already converted to apatitic phase by ultrastructural study of decalcified specimens. These structures were very similar to the components of bone nodules seen in intramembranous osteogenesis. It is postulated that the precursors of HA have an important role in intramembranous osteogenesis.calcium phosphate (Ca-P) compounds ; precursors ; hydroxyapatile ; bone formation ; bone matrix

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Macromolecular Aggregation States in Relation to Mineralization: The Collagen-Hydroxyapatite System as Studied in Vitro

Cited by 157 publications

References 16 publications

**Apert's syndrome: differential in vitro production of matrix macromolecules and its regulation by interleukins**

**Apert's syndrome: differential in vitro production of matrix macromolecules and its regulation by interleukins**

The genetic transformation of bone biology

Bone Formation on Synthetic Precursors of Hydroxyapatite.

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