T Cell-Expressed CD40L potentiates the bone anabolic activity of intermittent PTH treatment

Jerid W. Robinson, Jau Yi Li, Lindsey D. Walker, Abdul Malik Tyagi, Michael A. Reott, Mingcan Yu, Jonathan Adams, M. Neale Weitzmann, Roberto Pacifici

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)695-705
Number of pages11
JournalJournal of Bone and Mineral Research
Volume30
Issue number4
DOIs
StatePublished - Apr 1 2015

Keywords

  • BM
  • Bone Marrow
  • OB
  • Osteoblast
  • PPR
  • PTH
  • PTH/PTHRP Receptor
  • Parathyroid Hormone
  • SC
  • Stromal Cell

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