MT1-MMP modulates the mechanosensitivity of osteocytes

作者：Kulkarni Rishikesh N; Bakker Astrid D; Gruber Elisabeth V; Chae Thomas D; Veldkamp Joris B B; Klein Nulend Jenneke^*; Everts Vincent

来源：Biochemical and Biophysical Research Communications, 2012, 417(2): 824-829.

DOI：10.1016/j.bbrc.2011.12.045

• MT1-MMP
• Mechanosensitivity
• Osteocytes
• Pulsating fluid flow
• Mechanical loading

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. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;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.

• 出版日期2012-1-13