Tendon Cells Demonstrate Store‐Operated Calcium Entry Capacity and Differences in Calcium Signaling Through Aging

Abstract

Calcium is an important and ubiquitous second messenger, controlling a wide variety of cellular functions in virtually all cells in the mammalian body. In particular, calcium homeostasis is known to be a critical biomarker for tendon cell (tenocyte) behavior, serving as an essential feature of proper tenocyte function and mechano-transduction capability. However, the molecular mechanisms of how intracellular calcium levels are regulated within tenocytes, as well as the changes that these processes undergo through the aging process have remained largely unexplored. Using the ratiometric fluorescent calcium dye Fura-2, we showed for the first time evidence of store-operated calcium entry (SOCE) in primary tenocytes obtained from tail tendon fascicles of the mouse. In addition, since studies have shown that the process of aging yields a predominant decline in tissue and cell health, we further investigated calcium homeostasis in both young (4-6 months) and aged (20-22 months) mice to determine whether or not calcium regulation is altered through the process of aging. Overall, aged tenocytes demonstrated a reduced SOCE response and higher calcium “resting” levels, when compared to young tenocytes. This work shows for the first time, tenocyte capacity for SOCE, as well as differences in this process between younger and older cells, and opens new investigative avenues for tendon biology and potential treatments for tendon disorders.