T Cell–Expressed CD40L Potentiates the Bone Anabolic Activity of Intermittent PTH Treatment

JW Robinson, JY Li, LD Walker… - Journal of Bone and …, 2015 - academic.oup.com
JW Robinson, JY Li, LD Walker, AM Tyagi, MA Reott, M Yu, J Adams, MN Weitzmann…
Journal of Bone and Mineral Research, 2015academic.oup.com
ABSTRACT T cells are known to potentiate the bone anabolic activity of intermittent
parathyroid hormone (iPTH) treatment. One of the involved mechanisms is increased T cell
secretion of Wnt10b, a potent osteogenic Wnt ligand that activates Wnt signaling in stromal
cells (SCs). However, additional mechanisms might play a role, including direct interactions
between surface receptors expressed by T cells and SCs. Here we show that iPTH failed to
promote SC proliferation and differentiation into osteoblasts (OBs) and activate Wnt …
Abstract
T cells are known to potentiate the bone anabolic activity of intermittent parathyroid hormone (iPTH) treatment. One of the involved mechanisms is increased T cell secretion of Wnt10b, a potent osteogenic Wnt ligand that activates Wnt signaling in stromal cells (SCs). However, additional mechanisms might play a role, including direct interactions between surface receptors expressed by T cells and SCs. Here we show that iPTH failed to promote SC proliferation and differentiation into osteoblasts (OBs) and activate Wnt signaling in SCs of mice with a global or T cell–specific deletion of the T cell costimulatory molecule CD40 ligand (CD40L). Attesting to the relevance of T cell–expressed CD40L, iPTH induced a blunted increase in bone formation and failed to increase trabecular bone volume in CD40L–/– mice and mice with a T cell–specific deletion of CD40L. CD40L null mice exhibited a blunted increase in T cell production of Wnt10b and abrogated CD40 signaling in SCs in response to iPTH treatment. Therefore, expression of the T cell surface receptor CD40L enables iPTH to exert its bone anabolic activity by activating CD40 signaling in SCs and maximally stimulating T cell production of Wnt10b. © 2014 American Society for Bone and Mineral Research.
Oxford University Press