DMP1-Cre expressing cells mediate the gain in bone mass and strength, but not the increase in bone remodeling, induced by ligands of the parathyroid hormone receptor.

Authors

Nisreen Akel, Sasidhar Uppuganti, Jeff D Thostenson, Wyatt House, Kaitlyn Hapke, Gretel G Pellegrini, Joan Pizarro-Gómez, Shenyang Li, Meloney Cregor, Silvia Marino, Jeffry S Nyman, Teresita Bellido

Published in

Bone research. Volume 14. Issue 1. Jul 30, 2026. Epub Jul 30, 2026.

Abstract

Signaling downstream of the receptor of parathyroid hormone (PTH1R) exerts two major skeletal effects: increases bone remodeling and, when stimulated intermittently, induces bone anabolism. Osteocytes express the PTH1R and are critical for the action of teriparatide/parathyroid hormone 1-34 (PTH). However, it is unknown whether they also mediate the effects of abaloparatide (a 34 amino acid synthetic analog of human parathyroid hormone-related protein, ABL), and whether actions on osteocytes are required for the increase in remodeling and/or the bone gain induced by PTH/ABL in diabetes. We addressed these questions by treating with PTH or ABL control or diabetic (DM) mice lacking the PTH1R in DMP1-Cre expressing cells that targets all osteocytes (cKO). Both PTH and ABL increased bone mass and improved or corrected cortical and trabecular bone microarchitecture only in fl/fl littermates but not in cKO, control or DM mice. Further, PTH/ABL increased bone strength and microindentation resistance only in control or DM fl/fl mice. In contrast, PTH/ABL increased serum P1NP and bone formation on cancellous, periosteal and endocortical surfaces, in control or DM mice of both genotypes. Moreover, serum CTX and osteoclast surface were increased by PTH/ABL in fl/fl and cKO, control or DM mice. Thus, actions on DMP1-Cre expressing cells are required for bone gain, microarchitecture restoration, strength and resistance to fracture, exerted by PTH and ABL under physiological and DM conditions, but not for the increase in bone remodeling. These findings demonstrate the dissociation of bone gain from bone remodeling and reveal that actions on DMP1-Cre expressing cells drive the gain in bone mass and strength induced by PTH and ABL.

PMID:
42532988
Bibliographic data and abstract were imported from PubMed on 31 Jul 2026.

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