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.

Akel N, Uppuganti S, Thostenson JD, House W, Hapke K, Pellegrini GG, Pizarro-Gómez J, Li S, Cregor M, Marino S, Nyman JS, Bellido T

Bone research30 Jul 2026

PMID42532988PMCIDPMC13424361DOI10.1038/s41413-026-00555-zPepBankPUB-42532988

Download PDF PubMedAsk about this study

Jump to 16 results

Summary

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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study16

16 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In control or diabetic fl/fl mice, abaloparatide increased bone mass.
In plain wordsIn control or diabetic fl/fl mice, abaloparatide increased bone mass.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseBone mass in fl/fl mice
Study
mousen: not reported in source
Control or diabetic fl/fl and PTH1R conditional knockout mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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).
Show in the study text Report a problemFND-4253298801
02AnimalAnimal study (in vivo)Efficacy outcome
In control or diabetic cKO mice, abaloparatide did not increase bone mass.
In plain wordsIn control or diabetic cKO mice, abaloparatide did not increase bone mass.
Peptide
Abaloparatide (Tymlos)
Outcome
No significant changeBone mass in cKO mice
Study
mousen: not reported in source
Control or diabetic fl/fl and PTH1R conditional knockout mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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).
Show in the study text Report a problemFND-4253298802
03AnimalAnimal study (in vivo)Efficacy outcome
In control or diabetic fl/fl mice, abaloparatide improved or corrected cortical bone microarchitecture.
In plain wordsIn control or diabetic fl/fl mice, abaloparatide improved or corrected outer bone structure.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseCortical microarchitecture in fl/fl mice
Study
mousen: not reported in source
Control or diabetic fl/fl and PTH1R conditional knockout mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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).
Show in the study text Report a problemFND-4253298803
04AnimalAnimal study (in vivo)Efficacy outcome
In control or diabetic fl/fl mice, abaloparatide improved or corrected trabecular bone microarchitecture.
In plain wordsIn control or diabetic fl/fl mice, abaloparatide improved or corrected spongy bone structure.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseTrabecular microarchitecture in fl/fl mice
Study
mousen: not reported in source
Control or diabetic fl/fl and PTH1R conditional knockout mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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).
Show in the study text Report a problemFND-4253298804
05AnimalAnimal study (in vivo)Efficacy outcome
In control or diabetic cKO mice, abaloparatide did not improve cortical bone microarchitecture.
In plain wordsIn control or diabetic cKO mice, abaloparatide did not improve outer bone structure.
Peptide
Abaloparatide (Tymlos)
Outcome
No significant changeCortical microarchitecture in cKO mice
Study
mousen: not reported in source
Control or diabetic fl/fl and PTH1R conditional knockout mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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).
Show in the study text Report a problemFND-4253298805
06AnimalAnimal study (in vivo)Efficacy outcome
In control or diabetic cKO mice, abaloparatide did not improve trabecular bone microarchitecture.
In plain wordsIn control or diabetic cKO mice, abaloparatide did not improve spongy bone structure.
Peptide
Abaloparatide (Tymlos)
Outcome
No significant changeTrabecular microarchitecture in cKO mice
Study
mousen: not reported in source
Control or diabetic fl/fl and PTH1R conditional knockout mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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).
Show in the study text Report a problemFND-4253298806
07AnimalAnimal study (in vivo)Efficacy outcome
In control or diabetic fl/fl mice, abaloparatide increased bone strength.
In plain wordsIn control or diabetic fl/fl mice, abaloparatide increased bone strength.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseBone strength in fl/fl mice
Study
mousen: not reported in source
Control or diabetic fl/fl and PTH1R conditional knockout mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
Further, PTH/ABL increased bone strength and microindentation resistance only in control or DM fl/fl mice.
1 context sentence(design, population, supporting numbers)
Summary · context
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).
Show in the study text Report a problemFND-4253298807
08AnimalAnimal study (in vivo)Efficacy outcome
In control or diabetic cKO mice, abaloparatide did not increase bone strength.
In plain wordsIn control or diabetic cKO mice, abaloparatide did not increase bone strength.
Peptide
Abaloparatide (Tymlos)
Outcome
No significant changeBone strength in cKO mice
Study
mousen: not reported in source
Control or diabetic fl/fl and PTH1R conditional knockout mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
Further, PTH/ABL increased bone strength and microindentation resistance only in control or DM fl/fl mice.
1 context sentence(design, population, supporting numbers)
Summary · context
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).
Show in the study text Report a problemFND-4253298808
09AnimalAnimal study (in vivo)Efficacy outcome
In control or diabetic fl/fl mice, abaloparatide increased microindentation resistance.
In plain wordsIn control or diabetic fl/fl mice, abaloparatide increased bone resistance to indentation.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseMicroindentation resistance in fl/fl mice
Study
mousen: not reported in source
Control or diabetic fl/fl and PTH1R conditional knockout mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
Further, PTH/ABL increased bone strength and microindentation resistance only in control or DM fl/fl mice.
1 context sentence(design, population, supporting numbers)
Summary · context
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).
Show in the study text Report a problemFND-4253298809
10AnimalAnimal study (in vivo)Efficacy outcome
In control or diabetic cKO mice, abaloparatide did not increase microindentation resistance.
In plain wordsIn control or diabetic cKO mice, abaloparatide did not increase bone resistance to indentation.
Peptide
Abaloparatide (Tymlos)
Outcome
No significant changeMicroindentation resistance in cKO mice
Study
mousen: not reported in source
Control or diabetic fl/fl and PTH1R conditional knockout mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
Further, PTH/ABL increased bone strength and microindentation resistance only in control or DM fl/fl mice.
1 context sentence(design, population, supporting numbers)
Summary · context
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).
Show in the study text Report a problemFND-4253298810
11AnimalAnimal study (in vivo)Efficacy outcome
In control or diabetic mice of both genotypes, abaloparatide increased serum P1NP.
In plain wordsIn control or diabetic mice of both genotypes, abaloparatide increased a blood marker of bone formation.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseSerum P1NP
Study
mousen: not reported in source
Control or diabetic fl/fl and PTH1R conditional knockout mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
In contrast, PTH/ABL increased serum P1NP and bone formation on cancellous, periosteal and endocortical surfaces, in control or DM mice of both genotypes.
1 context sentence(design, population, supporting numbers)
Summary · context
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).
Show in the study text Report a problemFND-4253298811
12AnimalAnimal study (in vivo)Efficacy outcome
In control or diabetic mice of both genotypes, abaloparatide increased cancellous bone formation.
In plain wordsIn control or diabetic mice of both genotypes, abaloparatide increased spongy bone formation.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseCancellous bone formation
Study
mousen: not reported in source
Control or diabetic fl/fl and PTH1R conditional knockout mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
In contrast, PTH/ABL increased serum P1NP and bone formation on cancellous, periosteal and endocortical surfaces, in control or DM mice of both genotypes.
1 context sentence(design, population, supporting numbers)
Summary · context
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).
Show in the study text Report a problemFND-4253298812
13AnimalAnimal study (in vivo)Efficacy outcome
In control or diabetic mice of both genotypes, abaloparatide increased periosteal bone formation.
In plain wordsIn control or diabetic mice of both genotypes, abaloparatide increased bone formation on the outer surface.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreasePeriosteal bone formation
Study
mousen: not reported in source
Control or diabetic fl/fl and PTH1R conditional knockout mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
In contrast, PTH/ABL increased serum P1NP and bone formation on cancellous, periosteal and endocortical surfaces, in control or DM mice of both genotypes.
1 context sentence(design, population, supporting numbers)
Summary · context
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).
Show in the study text Report a problemFND-4253298813
14AnimalAnimal study (in vivo)Efficacy outcome
In control or diabetic mice of both genotypes, abaloparatide increased endocortical bone formation.
In plain wordsIn control or diabetic mice of both genotypes, abaloparatide increased bone formation on the inner cortical surface.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseEndocortical bone formation
Study
mousen: not reported in source
Control or diabetic fl/fl and PTH1R conditional knockout mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
In contrast, PTH/ABL increased serum P1NP and bone formation on cancellous, periosteal and endocortical surfaces, in control or DM mice of both genotypes.
1 context sentence(design, population, supporting numbers)
Summary · context
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).
Show in the study text Report a problemFND-4253298814
15AnimalAnimal study (in vivo)Efficacy outcome
In control or diabetic fl/fl and cKO mice, abaloparatide increased serum CTX.
In plain wordsIn control or diabetic fl/fl and cKO mice, abaloparatide increased a blood marker of bone breakdown.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseSerum CTX
Study
mousen: not reported in source
Control or diabetic fl/fl and PTH1R conditional knockout mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
Moreover, serum CTX and osteoclast surface were increased by PTH/ABL in fl/fl and cKO, control or DM mice.
1 context sentence(design, population, supporting numbers)
Summary · context
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).
Show in the study text Report a problemFND-4253298815
16AnimalAnimal study (in vivo)Efficacy outcome
In control or diabetic fl/fl and cKO mice, abaloparatide increased osteoclast surface.
In plain wordsIn control or diabetic fl/fl and cKO mice, abaloparatide increased the bone surface occupied by bone-resorbing cells.
Peptide
Abaloparatide (Tymlos)
Outcome
IncreaseOsteoclast surface
Study
mousen: not reported in source
Control or diabetic fl/fl and PTH1R conditional knockout mice
Outcome group
Bone and joint · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
Moreover, serum CTX and osteoclast surface were increased by PTH/ABL in fl/fl and cKO, control or DM mice.
1 context sentence(design, population, supporting numbers)
Summary · context
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).
Show in the study text Report a problemFND-4253298816

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
22 Oct 2026, 02:25 UTC
Study results updated
Version 1
21 Oct 2026, 18:59 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

MeSH terms

PepBank is a research reference. Talk to a doctor before you use any peptide.