T-Lymphocytes Enable Osteoblast Maturation During Early Phases of Fracture Repair

INTRODUCTION: The molecular and cellular regulation of fracture healing is not completely understood, yet such knowledge is critical to developing treatments to optimize bone repair and remodeling. One area of continued interest is osteoimmunology: studying the interactions between pathways of the immune system and their interplay with bone healing. Specifically, immunological regulation of the osteoblast (OB) has been a particularly poorly understood topic to date. While it is well known that there exists an interaction between OB and osteoclast (OC) cells through RANK-RANKL signaling, the role of lymphocytes and cytokines in OB biology during fracture healing remains unclear. To this end, mice lacking the recombinase activating genes 1 and 2 (Rag) were chosen as a model for studying this interaction as they are unable to form T-cell (TC) or B-cell (BC) receptors and hence, completely lack mature TC and BC lymphocytes. In turn, they are devoid of any lymphocytic sources of interleukins, providing a model of fracture healing in the complete absence of these factors. Previous literature is suggestive of a lymphocytic role in fracture healing, noting that mice lacking the subset of γδTCs develop better fracture calluses. The objective of this study is to use the Rag mouse to elucidate the physiological role of TCs in fracture healing, specifically on OB differentiation. It is hypothesized that TCs and/or their subtypes positively influence OBs leading to improved fracture healing.