Interaktion zwischen Muskel und Knochen – ein Wechselspiel zwischen Physik und Biologie

Zusammenfassung

Die balancierte und reziproke adaptive Interaktion zwischen Muskel und Knochen ist essenziell für die Fortbewegung von Organismen und die Erhaltung ihrer stabilen Form unter Vermeidung von Frakturen und Verletzungen. Muskeln erzeugen durch Kontraktion physikalische Kräfte, die auf die Muskulatur selbst und auf das stabilisierende Skelett wirken. Das Kraftniveau wird von der Gravitation und der Masse des eigenen Organismus bestimmt. Steigerung der Kräfte und Wiederholung der Reize haben anabole Wirkung, Immobilisation und Simulation von Mikro-Gravitation führen zum Verlust von Muskel und Knochen. Die Einwirkung physikalischer Kräfte auf Zellen wird in biochemische Signale umgesetzt und generiert biologische Effekte. Die molekularen Mechanismen des Mechanosensing und der Mechanotransduktion sind in den letzten 2–3 Dekaden sehr intensiv erforscht worden. Dehnung, Kompression und Flüssigkeitsströmung verursachen über Verbindungen durch Adhäsionsmoleküle an die Extrazellulärmatrix und zwischen den Zellen sowie über das Primäre Zilium eine „Second-messenger“-Aktivierung wie Kalzium-Einstrom, cAMP- und cGMP-Produktion und Aktivierung von Rezeptoren und Kinasen. Im Gefolge werden Transkriptionsfaktoren nukleotrop, die dann an DNA-responsive Steuerelemente binden und Transkription modulieren. Die Änderungen des Proteoms der Zelle führen zur vermehrten Bildung von Strukturproteinen zur Verstärkung des Zytoskeletts und der Zell-Zell-Adhäsion, sodass sich die Steifigkeit und die Rückstellkraft der Zelle und des Gewebes auf ein höheres Kraftniveau einstellen, ohne durch Ruptur oder Fraktur Schaden zu nehmen. Neben der physikalischen Interaktion durch die Kräfte des Muskels werden auch über Sekretionsprodukte von Muskel und Knochen Informationen ausgetauscht. Die Sekretionsprodukte initiieren und regulieren mit großen Überlappungen in ihrer Funktion die interaktive Adaptation und Regeneration in beiden Geweben. Neben der tonischen Produktion von Proteinen mit einer sekretorischen Sequenz können beide Gewebe auch auf mechanische Reize hin Vesikel abgeben, die als Fracht präsynthetisierte Rezeptoren, Wachstums- und Differenzierungsfaktoren und orchestrierende miRNAs transportieren können. Da weder Knochen noch Muskel echte endokrine Vesikel bilden können, werden Exosomen in die Zirkulation abgegeben. Ein auslösender Reiz dafür ist ein Kalzium-Einstrom als Folge von mechanischer Stimulation/Trainingsaktivität. Mit zunehmendem Wissen ergibt sich hier ein Bild der unerwartet intensiven Auswirkung mechanischer Kräfte auf die Zellbiologie und Biochemie von Geweben. Wir beginnen gerade, diese Auswirkungen in der Physiologie zu verstehen, während wir im Verständnis der Störungen einer gesunden Adaptation, z. B. im Sinne von Überlastung oder Trainingsresistenz, besonders bei chronischen Erkrankungen wie Osteoporose und Arthrose noch sehr am Anfang stehen.

Abstract

Balanced and reciprocal adaptive interaction between muscle and bone is essential for locomotion and for the maintenance of integrity of the organism in order to avoid ruptures and fractures. Contracting muscles produce physical forces that influence both the musculature itself and the stabilizing skeleton. Gravity and body mass define the power of forces. Escalation of power and repetitions of physical stimuli lead to anabolic effects in both tissues while immobilization, disuse and simulation of micro-gravity produce muscle and bone loss. The impact of physical strain on cells is translated into biochemical signals and generates biological effects. During the last 2–3 decades, the molecular mechanisms of mechanosensing and mechanotransduction have been intensely explored. Stretching, compression and fluid flow respectively set strain on adhesion molecules between cells and the extracellular matrix as well as on cell-cell interactions, thereby causing cell deformations and activation of calcium influx, cAMP and cGMP production and activation of kinases. In consequence, transcription factors acquire nucleotropy, bind to DNA-response elements and modulate transcription. Consecutive changes in the proteome result in enhanced production of structural proteins to fortify the architecture of the cytoskeleton and of cell adhesion. This enhances the stiffness and viscoelasticity of both the cell and the tissue composition in order to adapt to the higher level of power without injury. Besides the mere physical interaction through muscle forces both tissues also exchange information via secretory products of both muscle and bone. These products initiate and regulate interactive adaptation and regeneration with a great deal of functional overlap between tissues. Besides a tonic secretion of polypeptides with secretory domains, both tissues are also capable of secreting vesicles upon exercise that transport pre-synthesized receptors, growth and differentiation factors and miRNAs as a cargo. Since neither of both tissues is capable of producing true endocrine vesicles, they deliver exosomes into the circulation. One adequate stimulus for exosome delivery is calcium influx upon mechanical strain or exercise, respectively. With our steadily increasing knowledge, the evolving picture is an unexpectedly strong influence of mechanical forces on cellular biochemistry and cell biology of tissues. While we just begin to understand the physiology of mechanosensing and mechanotransduction as perfect tools for adaptation to environmental needs, our knowledge about the impact of alterations in this field, e. g. overload and exercise resistance, on chronic diseases like osteoporosis and osteoarthritis is still in its infancy.

Schlüsselwörter

Mechanotransduktion - Mechanobiologie - Bewegung - Training - Osteoporose - Sarkopenie

Key words

Mechanotransduction - mechanobiology - locomotion - exercise - osteoporosis - sarcopenia

Publication History

Received: 04 November 2019

Accepted: 19 November 2019

Article published online:
02 June 2020

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