Does Apo2L/TRAIL play any physiologic role in osteoclastogenesis?

Abstract

10. Yee L, Fanale M, Dimick K, et al. A phase 1B safety and pharmacokinetic (PK) study of recombinant human Apo2L/TRAIL in combination with rituximab in patients with low-grade non-Hodgkin lymphoma.

Combined therapy with the RANKL inhibitor RANK-Fc and rhApo2L/TRAIL/dulanermin reduces bone lesions and skeletal tumor burden in a model of breast cancer skeletal metastasis

“…38 Finally, Labrinidis et al found no direct effects of Apo2L/TRAIL on osteoclast differentiation and activity. 45 It is noteworthy that Labrinidis used clinical grade rhApo2L/TRAIL in their studies, which is in accordance with our studies. It has been established that different recombinant versions of Apo2L/TRAIL may yield a broad range of different biological activities and this could lead to a discrepancy in the results.…”

“…45,46 Our studies were not designed to directly address the role of rhApo2L/TRAIL on osteoclastogenesis, but rather the combined effects of RANK-Fc and rhApo2L/TRAIL on the growth of skeletal tumors. However, we did not see a significant effect of rhApo2L/TRAIL on serum TRAP5b levels.…”

Apo2L/TRAIL Inhibits Tumor Growth and Bone Destruction in a Murine Model of Multiple Myeloma

“…In this study, our detailed histomorphometric and micro-CT analysis of the contralateral non-tumor-bearing bones of Apo2L/TRAIL-treated animals showed no significant effect of Apo2L/TRAIL on any bone morphometric parameter. In contrast, treatment with the antiresorptive bisphosphonate zoledronic acid, which was used for comparison as a positive control, resulted in a significant increase in bone mass as expected (39). Recently, we reported on the effect of Apo2L/TRAIL on osteoclast differentiation and bone resorption using three independent in vitro models of osteoclastogenesis (39).…”

“…In contrast, treatment with the antiresorptive bisphosphonate zoledronic acid, which was used for comparison as a positive control, resulted in a significant increase in bone mass as expected (39). Recently, we reported on the effect of Apo2L/TRAIL on osteoclast differentiation and bone resorption using three independent in vitro models of osteoclastogenesis (39). We showed that Apo2L/TRAIL did not block RANKL-mediated osteoclast differentiation or bone resorption from human peripheral blood mononuclear cells or from the murine monocytic cell line, RAW264.7.…”

New insights into apoptosis signaling by Apo2L/TRAIL

“…Apo2L/ TRAIL binds to OPG, although with a lower affinity, and this has been proposed to regulate differentiation and survival of mature osteoclasts (Zauli et al, 2004(Zauli et al, , 2008Vitovski et al, 2007). However, considering that Apo2L/TRAIL-knockout mice are viable and develop normal bone density (Cretney et al, 2002;NewsomDavis et al, 2009), it remains unclear whether this ligand has a significant physiological role in regulating osteoclastogenesis (Labrinidis et al, 2008).…”