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Study · Animal study (in vivo) · 2018

22 results

Parathyroid hormone(1-34) and its analogs differentially modulate osteoblastic Rankl expression via PKA/SIK2/SIK3 and PP1/PP2A-CRTC3 signaling.

Ricarte FR, Le Henaff C, Kolupaeva VG, Gardella TJ, Partridge NC

The Journal of biological chemistry30 Oct 2018Cited by 58 (Europe PMC)

PMID30377251 (opens in a new tab)PMCIDPMC6311504 (opens in a new tab)DOI10.1074/jbc.ra118.004751 (opens in a new tab)PepBankPUB-30377251
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Summary

Osteoporosis can result from the loss of sex hormones and/or aging. Abaloparatide (ABL), an analog of parathyroid hormone-related protein (PTHrP(1-36)), is the second osteoanabolic therapy approved by the United States Food and Drug Administration after teriparatide (PTH(1-34)). All three peptides bind PTH/PTHrP receptor type 1 (PTHR1), but the effects of PTHrP(1-36) or ABL in the osteoblast remain unclear. We show that, in primary calvarial osteoblasts, PTH(1-34) promotes a more robust cAMP response than PTHrP(1-36) and ABL and causes a greater activation of protein kinase A (PKA) and cAMP response element-binding protein (CREB). All three peptides similarly inhibited sclerostin (Sost). Interestingly, the three peptides differentially modulated two other PKA target genes, c-Fos and receptor activator of NF-κB ligand (Rankl), and the latter both in vitro and in vivo Knockdown of salt-inducible kinases (SIKs) 2 and 3 and CREB-regulated transcription coactivator 3 (CRTC3), indicated that all three are part of the pathway that regulates osteoblastic Rankl expression. We also show that the peptides differentially regulate the nuclear localization of CRTC2 and CRTC3, and that this correlates with PKA activation. Moreover, inhibition of protein phosphatases 1 and 2A (PP1/PP2A) activity revealed that they play a major role in both PTH-induced Rankl expression and the effects of PTH(1-34) on CRTC3 localization. In summary, in the osteoblast, the effects of PTH(1-34), PTHrP(1-36), and ABL on Rankl are mediated by differential stimulation of cAMP/PKA signaling and by their downstream effects on SIK2 and -3, PP1/PP2A, and CRTC3.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study22

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

  1. 01AnimalAnimal study (in vivo)Mechanism

    In vivo, abaloparatide, PTH(1-34) and PTHrP(1-36) differentially modulated osteoblastic Rankl expression.

    In plain wordsIn animals, abaloparatide differed from the other peptides in its effects on osteoblast Rankl expression.

    Peptide
    Abaloparatide (Tymlos)
    Outcome
    MixedRankl expression in vivo
    Study

    n: not reported in source

    in vivo osteoblast response
    Comparator
    PTH(1-34) and PTHrP(1-36)
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Interestingly, the three peptides differentially modulated two other PKA target genes, c-Fos and receptor activator of NF-κB ligand (Rankl), and the latter both in vitro and in vivo
    1 context sentence
    Summary · context
    All three peptides bind PTH/PTHrP receptor type 1 (PTHR1), but the effects of PTHrP(1-36) or ABL in the osteoblast remain unclear.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In vivo, PTH(1-34), abaloparatide and PTHrP(1-36) differentially modulated osteoblastic Rankl expression.

    In plain wordsIn animals, PTH(1-34) differed from the other peptides in its effects on osteoblast Rankl expression.

    Peptide
    Teriparatide (PTH 1-34)
    Outcome
    MixedRankl expression in vivo
    Study

    n: not reported in source

    in vivo osteoblast response
    Comparator
    abaloparatide and PTHrP(1-36)
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Interestingly, the three peptides differentially modulated two other PKA target genes, c-Fos and receptor activator of NF-κB ligand (Rankl), and the latter both in vitro and in vivo
    1 context sentence
    Summary · context
    All three peptides bind PTH/PTHrP receptor type 1 (PTHR1), but the effects of PTHrP(1-36) or ABL in the osteoblast remain unclear.
  3. 03LabIn vitro (cells)Mechanism

    In primary calvarial osteoblasts, abaloparatide produced a weaker cAMP response than PTH(1-34).

    In plain wordsIn cells, abaloparatide produced a weaker cAMP response than PTH(1-34).

    Peptide
    Abaloparatide (Tymlos)
    Outcome
    DecreasecAMP response
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Comparator
    PTH(1-34)
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We show that, in primary calvarial osteoblasts, PTH(1-34) promotes a more robust cAMP response than PTHrP(1-36) and ABL and causes a greater activation of protein kinase A (PKA) and cAMP response element-binding protein (CREB).
  4. 04LabIn vitro (cells)Mechanism

    In primary calvarial osteoblasts, PTH(1-34) produced a stronger cAMP response than PTHrP(1-36) and abaloparatide.

    In plain wordsIn cells, PTH(1-34) produced a stronger cAMP response than PTHrP(1-36) and abaloparatide.

    Peptide
    Teriparatide (PTH 1-34)
    Outcome
    IncreasecAMP response
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Comparator
    PTHrP(1-36) and abaloparatide
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We show that, in primary calvarial osteoblasts, PTH(1-34) promotes a more robust cAMP response than PTHrP(1-36) and ABL and causes a greater activation of protein kinase A (PKA) and cAMP response element-binding protein (CREB).
  5. 05LabIn vitro (cells)Mechanism

    In primary calvarial osteoblasts, abaloparatide activated PKA less than PTH(1-34).

    In plain wordsIn cells, abaloparatide activated PKA less than PTH(1-34).

    Peptide
    Abaloparatide (Tymlos)
    Outcome
    DecreasePKA activation
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Comparator
    PTH(1-34)
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We show that, in primary calvarial osteoblasts, PTH(1-34) promotes a more robust cAMP response than PTHrP(1-36) and ABL and causes a greater activation of protein kinase A (PKA) and cAMP response element-binding protein (CREB).
  6. 06LabIn vitro (cells)Mechanism

    In primary calvarial osteoblasts, PTH(1-34) activated PKA more than PTHrP(1-36) and abaloparatide.

    In plain wordsIn cells, PTH(1-34) activated PKA more than PTHrP(1-36) and abaloparatide.

    Peptide
    Teriparatide (PTH 1-34)
    Outcome
    IncreasePKA activation
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Comparator
    PTHrP(1-36) and abaloparatide
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We show that, in primary calvarial osteoblasts, PTH(1-34) promotes a more robust cAMP response than PTHrP(1-36) and ABL and causes a greater activation of protein kinase A (PKA) and cAMP response element-binding protein (CREB).
  7. 07LabIn vitro (cells)Mechanism

    In primary calvarial osteoblasts, abaloparatide activated CREB less than PTH(1-34).

    In plain wordsIn cells, abaloparatide activated CREB less than PTH(1-34).

    Peptide
    Abaloparatide (Tymlos)
    Outcome
    DecreaseCREB activation
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Comparator
    PTH(1-34)
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We show that, in primary calvarial osteoblasts, PTH(1-34) promotes a more robust cAMP response than PTHrP(1-36) and ABL and causes a greater activation of protein kinase A (PKA) and cAMP response element-binding protein (CREB).
  8. 08LabIn vitro (cells)Mechanism

    In primary calvarial osteoblasts, PTH(1-34) activated CREB more than PTHrP(1-36) and abaloparatide.

    In plain wordsIn cells, PTH(1-34) activated CREB more than PTHrP(1-36) and abaloparatide.

    Peptide
    Teriparatide (PTH 1-34)
    Outcome
    IncreaseCREB activation
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Comparator
    PTHrP(1-36) and abaloparatide
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We show that, in primary calvarial osteoblasts, PTH(1-34) promotes a more robust cAMP response than PTHrP(1-36) and ABL and causes a greater activation of protein kinase A (PKA) and cAMP response element-binding protein (CREB).
  9. 09LabIn vitro (cells)Mechanism

    In osteoblasts, abaloparatide inhibited sclerostin similarly to PTH(1-34) and PTHrP(1-36).

    In plain wordsIn cells, abaloparatide inhibited sclerostin similarly to PTH(1-34) and PTHrP(1-36).

    Peptide
    Abaloparatide (Tymlos)
    Outcome
    No significant changeSclerostin expression
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Comparator
    PTH(1-34) and PTHrP(1-36)
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    All three peptides similarly inhibited sclerostin (Sost).
    1 context sentence
    Summary · context
    All three peptides bind PTH/PTHrP receptor type 1 (PTHR1), but the effects of PTHrP(1-36) or ABL in the osteoblast remain unclear.
  10. 10LabIn vitro (cells)Mechanism

    In osteoblasts, PTH(1-34) inhibited sclerostin similarly to abaloparatide and PTHrP(1-36).

    In plain wordsIn cells, PTH(1-34) inhibited sclerostin similarly to abaloparatide and PTHrP(1-36).

    Peptide
    Teriparatide (PTH 1-34)
    Outcome
    No significant changeSclerostin expression
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Comparator
    abaloparatide and PTHrP(1-36)
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    All three peptides similarly inhibited sclerostin (Sost).
    1 context sentence
    Summary · context
    All three peptides bind PTH/PTHrP receptor type 1 (PTHR1), but the effects of PTHrP(1-36) or ABL in the osteoblast remain unclear.
  11. 11LabIn vitro (cells)Mechanism

    In osteoblasts, abaloparatide and the other tested peptides differentially regulated CRTC2 nuclear localization, which correlated with PKA activation.

    In plain wordsIn cells, abaloparatide and the other tested peptides differed in CRTC2 nuclear localization effects, which correlated with PKA activation.

    Peptide
    Abaloparatide (Tymlos)
    Outcome
    MixedCRTC2 nuclear localization
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Comparator
    PTH(1-34) and PTHrP(1-36)
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We also show that the peptides differentially regulate the nuclear localization of CRTC2 and CRTC3, and that this correlates with PKA activation.
    1 context sentence
    Summary · context
    All three peptides bind PTH/PTHrP receptor type 1 (PTHR1), but the effects of PTHrP(1-36) or ABL in the osteoblast remain unclear.
  12. 12LabIn vitro (cells)Mechanism

    In osteoblasts, PTH(1-34) and the other tested peptides differentially regulated CRTC2 nuclear localization, which correlated with PKA activation.

    In plain wordsIn cells, PTH(1-34) and the other tested peptides differed in CRTC2 nuclear localization effects, which correlated with PKA activation.

    Peptide
    Teriparatide (PTH 1-34)
    Outcome
    MixedCRTC2 nuclear localization
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Comparator
    abaloparatide and PTHrP(1-36)
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We also show that the peptides differentially regulate the nuclear localization of CRTC2 and CRTC3, and that this correlates with PKA activation.
    1 context sentence
    Summary · context
    All three peptides bind PTH/PTHrP receptor type 1 (PTHR1), but the effects of PTHrP(1-36) or ABL in the osteoblast remain unclear.
  13. 13LabIn vitro (cells)Mechanism

    In osteoblasts, abaloparatide, PTH(1-34) and PTHrP(1-36) differentially modulated c-Fos expression.

    In plain wordsIn cells, abaloparatide differed from the other peptides in its effects on c-Fos expression.

    Peptide
    Abaloparatide (Tymlos)
    Outcome
    Mixedc-Fos expression
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Comparator
    PTH(1-34) and PTHrP(1-36)
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Interestingly, the three peptides differentially modulated two other PKA target genes, c-Fos and receptor activator of NF-κB ligand (Rankl), and the latter both in vitro and in vivo
    1 context sentence
    Summary · context
    All three peptides bind PTH/PTHrP receptor type 1 (PTHR1), but the effects of PTHrP(1-36) or ABL in the osteoblast remain unclear.
  14. 14LabIn vitro (cells)Mechanism

    In osteoblasts, PTH(1-34), abaloparatide and PTHrP(1-36) differentially modulated c-Fos expression.

    In plain wordsIn cells, PTH(1-34) differed from the other peptides in its effects on c-Fos expression.

    Peptide
    Teriparatide (PTH 1-34)
    Outcome
    Mixedc-Fos expression
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Comparator
    abaloparatide and PTHrP(1-36)
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Interestingly, the three peptides differentially modulated two other PKA target genes, c-Fos and receptor activator of NF-κB ligand (Rankl), and the latter both in vitro and in vivo
    1 context sentence
    Summary · context
    All three peptides bind PTH/PTHrP receptor type 1 (PTHR1), but the effects of PTHrP(1-36) or ABL in the osteoblast remain unclear.
  15. 15LabIn vitro (cells)Mechanism

    In osteoblasts in vitro, abaloparatide, PTH(1-34) and PTHrP(1-36) differentially modulated Rankl expression.

    In plain wordsIn cells, abaloparatide differed from the other peptides in its effects on Rankl expression.

    Peptide
    Abaloparatide (Tymlos)
    Outcome
    MixedRankl expression in vitro
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Comparator
    PTH(1-34) and PTHrP(1-36)
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Interestingly, the three peptides differentially modulated two other PKA target genes, c-Fos and receptor activator of NF-κB ligand (Rankl), and the latter both in vitro and in vivo
    1 context sentence
    Summary · context
    All three peptides bind PTH/PTHrP receptor type 1 (PTHR1), but the effects of PTHrP(1-36) or ABL in the osteoblast remain unclear.
  16. 16LabIn vitro (cells)Mechanism

    In osteoblasts in vitro, PTH(1-34), abaloparatide and PTHrP(1-36) differentially modulated Rankl expression.

    In plain wordsIn cells, PTH(1-34) differed from the other peptides in its effects on Rankl expression.

    Peptide
    Teriparatide (PTH 1-34)
    Outcome
    MixedRankl expression in vitro
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Comparator
    abaloparatide and PTHrP(1-36)
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Interestingly, the three peptides differentially modulated two other PKA target genes, c-Fos and receptor activator of NF-κB ligand (Rankl), and the latter both in vitro and in vivo
    1 context sentence
    Summary · context
    All three peptides bind PTH/PTHrP receptor type 1 (PTHR1), but the effects of PTHrP(1-36) or ABL in the osteoblast remain unclear.
  17. 17LabIn vitro (cells)Mechanism

    In osteoblasts, abaloparatide and the other tested peptides differentially regulated CRTC3 nuclear localization, which correlated with PKA activation.

    In plain wordsIn cells, abaloparatide and the other tested peptides differed in CRTC3 nuclear localization effects, which correlated with PKA activation.

    Peptide
    Abaloparatide (Tymlos)
    Outcome
    MixedCRTC3 nuclear localization
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Comparator
    PTH(1-34) and PTHrP(1-36)
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We also show that the peptides differentially regulate the nuclear localization of CRTC2 and CRTC3, and that this correlates with PKA activation.
    1 context sentence
    Summary · context
    All three peptides bind PTH/PTHrP receptor type 1 (PTHR1), but the effects of PTHrP(1-36) or ABL in the osteoblast remain unclear.
  18. 18LabIn vitro (cells)Mechanism

    In osteoblasts, PTH(1-34) and the other tested peptides differentially regulated CRTC3 nuclear localization, which correlated with PKA activation.

    In plain wordsIn cells, PTH(1-34) and the other tested peptides differed in CRTC3 nuclear localization effects, which correlated with PKA activation.

    Peptide
    Teriparatide (PTH 1-34)
    Outcome
    MixedCRTC3 nuclear localization
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Comparator
    abaloparatide and PTHrP(1-36)
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We also show that the peptides differentially regulate the nuclear localization of CRTC2 and CRTC3, and that this correlates with PKA activation.
    1 context sentence
    Summary · context
    All three peptides bind PTH/PTHrP receptor type 1 (PTHR1), but the effects of PTHrP(1-36) or ABL in the osteoblast remain unclear.

Studies that did not test the peptide alone4

In this study, the peptide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking the peptide.

  1. 19LabNot a test of Abaloparatide (Tymlos) aloneIn vitro (cells)Mechanism

    In osteoblasts, knockdown experiments implicated SIK2, SIK3 and CRTC3 in regulation of Rankl expression during peptide responses.

    In plain wordsIn cells, gene knockdown linked SIK2, SIK3 and CRTC3 to control of Rankl expression.

    Peptide
    Abaloparatide (Tymlos)
    Outcome
    Not applicableRankl regulatory pathway
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Outcome group
    Receptor activity and mechanism · Musculoskeletal

    Source sentences

    Summary
    Knockdown of salt-inducible kinases (SIKs) 2 and 3 and CREB-regulated transcription coactivator 3 (CRTC3), indicated that all three are part of the pathway that regulates osteoblastic Rankl expression.

    In this study, Abaloparatide (Tymlos) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Abaloparatide (Tymlos).

  2. 20LabNot a test of Teriparatide (PTH 1-34) aloneIn vitro (cells)Mechanism

    In osteoblasts, knockdown experiments implicated SIK2, SIK3 and CRTC3 in regulation of Rankl expression during peptide responses.

    In plain wordsIn cells, gene knockdown linked SIK2, SIK3 and CRTC3 to control of Rankl expression.

    Peptide
    Teriparatide (PTH 1-34)
    Outcome
    Not applicableRankl regulatory pathway
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Outcome group
    Receptor activity and mechanism · Musculoskeletal

    Source sentences

    Summary
    Knockdown of salt-inducible kinases (SIKs) 2 and 3 and CREB-regulated transcription coactivator 3 (CRTC3), indicated that all three are part of the pathway that regulates osteoblastic Rankl expression.

    In this study, Teriparatide (PTH 1-34) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Teriparatide (PTH 1-34).

  3. 21LabNot a test of Teriparatide (PTH 1-34) aloneIn vitro (cells)Mechanism

    In osteoblasts, phosphatase inhibition implicated PP1/PP2A in PTH-induced Rankl expression.

    In plain wordsIn cells, phosphatase inhibition linked PP1/PP2A to PTH-induced Rankl expression.

    Peptide
    Teriparatide (PTH 1-34)
    Outcome
    Not applicablePhosphatase contribution to PTH-induced Rankl expression
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Outcome group
    Receptor activity and mechanism · Musculoskeletal

    Source sentences

    Summary
    Moreover, inhibition of protein phosphatases 1 and 2A (PP1/PP2A) activity revealed that they play a major role in both PTH-induced Rankl expression and the effects of PTH(1-34) on CRTC3 localization.

    In this study, Teriparatide (PTH 1-34) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Teriparatide (PTH 1-34).

  4. 22LabNot a test of Teriparatide (PTH 1-34) aloneIn vitro (cells)Mechanism

    In osteoblasts, phosphatase inhibition implicated PP1/PP2A in the effects of PTH(1-34) on CRTC3 localization.

    In plain wordsIn cells, phosphatase inhibition linked PP1/PP2A to PTH effects on CRTC3 localization.

    Peptide
    Teriparatide (PTH 1-34)
    Outcome
    Not applicablePhosphatase contribution to PTH-induced CRTC3 localization
    Study

    n: not reported in source

    primary calvarial osteoblasts
    Outcome group
    Receptor activity and mechanism · Musculoskeletal

    Source sentences

    Summary
    Moreover, inhibition of protein phosphatases 1 and 2A (PP1/PP2A) activity revealed that they play a major role in both PTH-induced Rankl expression and the effects of PTH(1-34) on CRTC3 localization.

    In this study, Teriparatide (PTH 1-34) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Teriparatide (PTH 1-34).

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.

  1. Version 3Current

    22 Oct 2026, 02:25 UTC

    Study results updated

  2. Version 2

    21 Oct 2026, 18:59 UTC

    Study data updated · source update from Europe PMC

  3. Version 1

    21 Oct 2026, 18:59 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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