Wnt-Signalwege im Knochenstoffwechsel

M. Peterlik

doi:10.1055/s-0037-1619993

Osteologie, Table of Contents

Osteologie 2011; 20(03): 197-202
DOI: 10.1055/s-0037-1619993

Knochenzellbiologie und Osteoporosetherapie

Schattauer GmbH

Wnt-Signalwege im Knochenstoffwechsel

Wnt signaling pathways and bone turnover

Authors

M. Peterlik

¹Institut für Pathophysiologie, Medizinische Universität Wien, Österreich

Abstract

Zusammenfassung

Sowohl der „kanonische” Wnt-Signalweg mit β-Catenin als terminalem Effektor als auch der „nicht-kanonische” Wnt/Ca⁺⁺-Weg, in dem intrazelluläres Ca⁺⁺ als „second messenger” fungiert, spielen beim kontinuierlichen Umbau des Knochens („bone remodeling”) eine wichtige Rolle: Sie koordinieren die einzelnen Phasen der Knochenneubildung (von der osteogenen Differenzierung pluripotenter mesenchymaler Stammzellen bis zur Bildung einer mineralisierten Matrix durch reife Osteoblasten bzw. Osteozyten), regulieren aber auch die Differenzierung und Aktivierung von Osteoklasten. Aufbau und Erhalt der Knochenmasse ist weitgehend genetisch determiniert, und zwar durch das Ausmaß der Expression der für die einzelnen Komponenten der Wnt/β-Catenin-Signalkaskade, insbesondere für den Wnt-Korezeptor LRP5, kodierenden Gene. Sowohl über die Schnittstellen mit anderen Signalwegen, die z. B. von RANK/ RANKL, PTH, 1,25-(OH)₂D₃/VDR oder Ca⁺⁺/CaR aktiviert werden, als auch durch Blockade der Wnt-Inhibitoren Dkk-1 und Sklerostin ergeben sich zahlreiche Möglichkeiten, die Effektivität der Wnt/β-Catenin-Signalkaskade positiv zu beeinflussen, was zur Prävention und Therapie der verschiedenen Formen der Osteoporose genutzt werden kann.

Summary

Both the “canonical” Wnt signaling pathway with β-catenin as its key downstream effector as well as the “non-canonical” Wnt/Ca⁺⁺ pathway, which uses intracellular Ca⁺⁺ as “second messenger”, play a key role in the control of bone remodeling. The Wnt signaling cascades coordinate the multiple phases in the process of bone formation (from osteogenic differentiation of pluripotent mesenchymal stem cells to matrix maturation and mineralization by fully differentiated osteoblasts and osteocytes), and also regulate differentiation and activation of osteoclasts. Accrual and maintenance of bone mass is genetically determined, mainly through expression of the genes that encode the components of the Wnt/β-catenin signaling pathway, particularly the Wnt co-receptor LRP5. Modulation of efficiency of Wnt-activated pathways, e. g. by costimulatory signals from pathways activated by RANK/RANKL, PTH, 1,25-(OH)₂D₃/VDR, and Ca⁺⁺/CaR, or by blocking Wnt-Inhibitors like Dkk-1 and sclerostin, respectively, provides a means for prevention and therapy of primary and secondary osteoporosis.

Schlüsselwörter

β-Catenin - Vitamin D - „Calcium-sensing”-Rezeptor - osteogene Differenzierung

Keywords

β-Catenin - vitamin D - calcium-sensing receptor - osteogenic differentiation

Full Text

References

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