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Osteoblasten

Zelluläre und molekulare Regulationsmechanismen in der Frakturheilung

Osteoblasts

Cellular and molecular regulatory mechanisms in fracture healing

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Zusammenfassung

Das Knochengewebe besitzt eine einzigartige Fähigkeit zur Regeneration und ist in der Lage, mechanische und metabolische Stimuli in biologische Antwort umzuwandeln. Die korrekte Regulation der Osteoblastendifferenzierung während der Frakturheilung ist komplex und in ihrer Gesamtheit noch nicht verstanden. Die Transkriptionsfaktoren RUNX2 und SP7 sind von besonderer Bedeutung und können als Mastergene der Osteoblastendifferenzierung betrachtet werden. Der kanonische WNT-Signalweg spielt sowohl während des Knochenwachstums als auch in der Frakturheilung eine essenzielle Rolle für die Aktivierung der osteoblastären Differenzierungsvorgänge. Experimentelle Studien konnten nachweisen, dass eine Suppression des WNT-Signalweges während der Frakturheilung eine signifikante Reduktion der Knochenbildung zur Folge hat. Die BMP2-vermittelte Aktivierung der Osteogenese ist ebenfalls von der korrekten WNT-Signalgebung abhängig. Die Patienten mit therapierefraktären Pseudarthrosen weisen nicht nur eine reduzierte Anzahl und Differenzierungskapazität der Osteoprogenitorzellen auf, sondern zeigen auch eine signifikant reduzierte Genexpression zahlreicher Faktoren der WNT-Signalkaskade auf. Die Erforschung des WNT-Signalweges könnte neue Perspektiven in der Behandlung der Knochenbruchheilungsstörungen und für das „tissue engineering“ des Knochengewebes eröffnen.

Abstract

Bone tissue possesses a unique regeneration ability, translating mechanical and metabolic stimuli into a biological response. The perpetual regeneration processes allow continuous self-renewal and adaptation to prevailing mechanical forces. The complex regulation of osteoblastic differentiation during fracture repair has not been completely defined. Two different transcription factors – RUNX2 and SP7 – are considered to be master genes of osteoblastic differentiation. Furthermore, the canonical WNT pathway plays an essential role in the activation of osteoblastic differentiation during both bone growth and fracture healing. Studies of fracture healing have revealed that downregulation of the WNT pathway causes a significant reduction in new bone formation. Moreover, correct WNT signalling is also required for BMP2-induced bone formation. There is increasing evidence that patients who develop recalcitrant fracture nonunions exhibit not only reduced numbers and differentiation capacity of osteogenic progenitors but also a significant downregulation of numerous factors in the WNT pathway. Therefore, better understanding of the WNT regulatory mechanisms could reveal new strategies for the treatment of delayed fracture healing and for the tissue engineering of bone.

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Interessenkonflikt

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Authors and Affiliations

  1. BiomaTiCS Group, Zentrum für Unfallchirurgie und Orthopädie, Universitätsmedizin, Johannes-Gutenberg-Universität, Langenbeckstraße 1, 55101, Mainz, Deutschland

    A. Hofmann, S.G. Mattyasovszky, C. Brüning, U. Ritz, I. Mehling & P.M. Rommens

  2. Orthopädische Universitätsklinik Friedrichsheim gGmbH, Frankfurt a. M., Deutschland

    A. Meurer

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  1. A. Hofmann
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  2. S.G. Mattyasovszky
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Correspondence to A. Hofmann.

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Gefördert durch Stiftung für Innovation Rheinland Pfalz (15202–38 62 61/577) und Deutsche Forschungsgesellschaft HO 4309/1–1.

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Hofmann, A., Mattyasovszky, S., Brüning, C. et al. Osteoblasten. Orthopäde 38, 1009–1019 (2009). https://doi.org/10.1007/s00132-009-1488-5

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