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torsdag 16 oktober 2014

Kollageeni. Luun ja dentiinin orgaanisesta aineesta on kollageenia suurin osa ( 90 %)

Luun ja dentiinin ORGAANINEN FAASI ( 30 % luusta)

KOLLAGEENI ( 90 % orgaanisista komponenteista)
Kollageeneja on iso perhe, 38 geenia koodaa näitä multimeerisiä proteiineja tuottaen 20 erilaista kypsää kollageenia.Päätyyppi kollageenia kovissa mineralisoituvissa kudoksissa on kollageeni I. Se muodostuu kolmoishelixrakenteella kahdella alfa1- ja yhdellä alfa2-ketjulla. Tämä modifioituu posttranslationaalisesti fosforylaatioilla, hydroksylaatioilla ja sulfaatioilla, jolloin kolmoisrakenne edelleen monimutkaistuu. Polymeeri erittyy prekursorinaan peptidiulokkeet molemmissa päissään ( N- ja C-terminaaleissaan).
Kaikkien ketjujen tulee olla aivan tarkasti järjestyksessä. Siksi yhdenkin ketjun mutaatiolla on kauaskantoiset seuraukset luukudokseen. Kollageenityypin I mutaatiot johtavat heterogeeniseen puutteelliseen luutumiseen, osteogenesis imperfecta,”brittle bone disease”. Koska kollageenin tulee toimia mineraalien saostumisessa alustana, template, on arveltu eräiden osteoporoosimuotojen taustana myös  piilevän kollageeni-I.ketjun geenien rakenteellisen mutaation.
Heti solun ulkopuolella kollageenin tripletti modifioituu, kovalentteja sidoksia muodostuu, erot kovan ja pehmeän kudoksen välillä tulevat esiin. Tämä poikkisidosten muodostamiskyky antaa luulle sen tyypillisen sitkeyden. Kollageenilla on vaikutuksia solufunktioihin, apoptoosiin, soluproliferaatioon ja differentioitumiseen monimutkaisen kontrollijärjestelmän kautta  Se signaloi solupinnalta tumaan.

  • LÄHDE: 

    (1)  SOMOGYI-GANSS Ester Novel non-collagenous modulators of biomineralization in bone and dentin ( 2004, KI, Stockholm) ISBN 91-7140-101-6

  • (2) Sharpeyn säikeet ovat kollageeniä. Niistä erikseen artikkeli.

  • Front Endocrinol (Lausanne). 2012 Aug 9;3:98. doi: 10.3389/fendo.2012.00098. eCollection 2012. Periosteal Sharpey's fibers: a novel bone matrix regulatory system?
Sharpey's "perforating" fibers (SF) are well known skeletally in tooth anchorage. Elsewhere they provide anchorage for the periosteum and are less well documented.

 Immunohistochemistry has transformed their potential significance by identifying their collagen type III (CIII) content and enabling their mapping in domains as permeating arrays of fibers (5-25 μ thick), protected from osteoclastic resorption by their poor mineralization.

 As periosteal extensions they are crucial in early skeletal development and central to intramembranous bone healing, providing unique microanatomical avenues for musculoskeletal exchange, their composition (e.g., collagen type VI, elastin, tenascin) combined with a multiaxial pattern of insertion suggesting a role more complex than attachment alone would justify.

 A proportion permeate the cortex to the endosteum (and beyond), fusing into a CIII-rich osteoid layer (<2 μ thick) encompassing all resting surfaces, and with which they apparently integrate into a PERIOSTEAL-SHARPEY FIBER-ENDOSTEUM (PSE) structural continuum.

This intraosseous system behaves in favor of bone loss or gain depending upon extraneous stimuli (i.e., like Frost's hypothetical "mechanostat"). Thus, the birefringent fibers are sensitive to humoral factors (e.g., estrogen causes retraction, rat femur model), physical activity (e.g., running causes expansion, rat model), aging (e.g., causes fragmentation, pig mandible model), and pathology (e.g., atrophied in osteoporosis, hypertrophied in osteoarthritis, human proximal femur), and with encroaching mineral particles hardening the usually soft parts. In this way the unobtrusive periosteal SF network may regulate bone status, perhaps even contributing to predictable "hotspots" of trabecular disconnection, particularly at sites of tension prone to fatigue, and with the network deteriorating significantly before bone matrix loss.

KEYWORDS:

collagen type III; collagen type VI; elastin; endosteal membrane; matrix biochemical domains; skeletal aging; tenascin

Free PMC Article

 collagen type VI, elastin, tenascin) combined with a multiaxial pattern of insertion suggesting a role more complex than attachment alone would justify.
 A proportion permeate the cortex to the endosteum (and beyond), fusing into a CIII-rich osteoid layer (<2 μ thick) encompassing all resting surfaces, and with which they apparently integrate into a PERIOSTEAL-SHARPEY FIBER-ENDOSTEUM (PSE) structural continuum. This intraosseous system behaves in favor of bone loss or gain depending upon extraneous stimuli (i.e., like Frost’s hypothetical “mechanostat”). Thus, the birefringent fibers are sensitive to humoral factors (e.g., estrogen causes retraction, rat femur model), physical activity (e.g., running causes expansion, rat model), aging (e.g., causes fragmentation, pig mandible model), and pathology (e.g., atrophied in osteoporosis, hypertrophied in osteoarthritis, human proximal femur), and with encroaching mineral particles hardening the usually soft parts. In this way the unobtrusive periosteal SF network may regulate bone status, perhaps even contributing to predictable “hotspots” of trabecular disconnection, particularly at sites of tension prone to fatigue, and with the network deteriorating significantly before bone matrix loss.

Keywords: collagen type III, collagen type VI, tenascin, elastin, matrix biochemical domains, skeletal aging, endosteal membrane
FIGURE 3
Diagram showing (A) a stylized CIII/CVI-rich periosteal Sharpey’s fiber with adherent beaded chains of tenascin and encircled by a coil of elastin, and (B) tracings of the same coarse fibers (about 15 μm diameter) in cross section showing ...
There now follows seven reasons why the Sharpey’s fiber network may act as an extracellular regulatory system in bone. Its candidature has been a lengthy one. Though not assigned as such, elements of the trabecular framework proposed below probably commenced in the seventeenth century at the dawn of microscopy with descriptions by Clopton Havers (Dobson, 1952) of penetrating “fibrillae,” thereby possibly preceding Sharpey himself. The precise nature of the musculoskeletal exchange mechanism instigated remains to be established, for example, a piezoelectric phenomenon (the piezoelectric modulus of tendon is apparently 30-fold that of bone; Marino and Becker, 1971) or one involving stress-regulated excitatory amino acids analogous to neural pathways (Mason et al., 1997) may be considered; there is also evidence that the ligaments with which the Sharpey’s fibers integrate may function as proprioceptors (Johansson et al., 1991).

SHARPEY’S FIBERS IN FETAL BONE DEVELOPMENT (FIBRONECTIN AND TENASCIN FACTORS)

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