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Biochem Biophys Res Commun ; 417(2): 824-9, 2012 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-22202174

RESUMEN

Membrane-type matrix metalloproteinase-1 (MT1-MMP) is expressed by mechanosensitive osteocytes and affects bone mass. The extracellular domain of MT1-MMP is connected to extracellular matrix, while its intracellular domain is a strong modulator of cell signaling. In theory MT1-MMP could thus transduce mechanical stimuli into a chemical response. We hypothesized that MT1-MMP plays a role in the osteocyte response to mechanical stimuli. MT1-MMP-positive and knockdown (siRNA) MLO-Y4 osteocytes were mechanically stimulated with a pulsating fluid flow (PFF). Focal adhesions were visualized by paxillin immunostaining. Osteocyte number, number of empty lacunae, and osteocyte morphology were measured in long bones of MT1-MMP(+/+) and MT1-MMP(-/-) mice. PFF decreased MT1-MMP mRNA and protein expression in MLO-Y4 osteocytes, suggesting that mechanical loading may affect pericellular matrix remodeling by osteocytes. MT1-MMP knockdown enhanced NO production and c-jun and c-fos mRNA expression in response to PFF, concomitantly with an increased number and size of focal adhesions, indicating that MT1-MMP knockdown osteocytes have an increased sensitivity to mechanical loading. Osteocytes in MT1-MMP(-/-) bone were more elongated and followed the principle loading direction, suggesting that they might sense mechanical loading. This was supported by a lower number of empty lacunae in MT1-MMP(-/-) bone, as osteocytes lacking mechanical stimuli tend to undergo apoptosis. In conclusion, mechanical stimulation decreased MT1-MMP expression by MLO-Y4 osteocytes, and MT1-MMP knockdown increased the osteocyte response to mechanical stimulation, demonstrating a novel and unexpected role for MT1-MMP in mechanosensing.


Asunto(s)
Metaloproteinasa 14 de la Matriz/fisiología , Mecanotransducción Celular/fisiología , Osteocitos/fisiología , Animales , Adhesiones Focales/enzimología , Adhesiones Focales/genética , Adhesiones Focales/fisiología , Técnicas de Silenciamiento del Gen , Metaloproteinasa 14 de la Matriz/genética , Mecanotransducción Celular/genética , Ratones , Ratones Mutantes , Osteocitos/citología , Osteocitos/enzimología , Flujo Pulsátil , ARN Interferente Pequeño/genética , Estrés Mecánico
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