| Transduction of mechanical stimuli in tenocytes is important for maintaining homeostasis and enhancing healing. Mechanotransduction involves multiple mechanisms including gap junctions and intercellular communication, G proteins, ion channels, and second messengers such as calcium. Additionally, biochemical mediators including growth factors, hormones, and catecholamines, such as norepinephrine (NE), help mediate tissue growth, development, and repair. Therefore, the purpose of these studies was to investigate the effects of mechanical loading (cyclic strain) and biochemical mediators (NE) on intercellular communication in tenocytes. It was hypothesized that strain measured at the cellular level would equal that measured at the deformable substrate. Secondly, it was hypothesized that cyclic strain would upregulate the expression of connexin 43 (Cx43), the principal protein of gap junctions in tenocytes. Thirdly, it was hypothesized that avian tenocytes express adrenoceptors and respond to NE by increasing intracellular calcium concentration ([Ca2+]ic. Finally, it was hypothesized that strain and NE together would produce an adaptive response in intercellular communication.;The local strains measured within cultured tenocytes were 35% to 65% of the applied equibiaxial and uniaxial substrate strain, respectively. In an acute response, avian tendon internal fibroblasts stretched at 1%, 3%, or 5% substrate elongation at 1 Hz for various times upregulated Cx43 mRNA expression by 6 hours of strain and returned to control levels by 12 hours. Cx43 protein was upregulated by 6 hours of strain and 1 hour of rest. Additionally, functional coupling between tenocytes was increased.;Avian tenocytes expressed both alpha1A- and alpha 1B-adrenoceptor subtypes and increased [Ca2+]ic in response to NE. Only the presence of an alpha1A-adrenoceptor antagonist significantly reduced this Ca2+ response. In an adaptive response, tenocytes stretched at 3.5% elongation, 1 Hz for 30 min a day for 9 days in the presence of NE increased cell-cell communication to neighboring cells as determined by Ca2+ wave propagation and dye-coupling.;Results of these studies indicated that tenocytes subjected to strain alone or with NE increased intercellular communication. Norepinephrine and load together could augment cell proliferation or mediate healing in tendon. Taken together, these data further illustrate the importance of both the humoral and mechanical environments in tendon. |
