The selective TrkA agonist, gambogic amide, promotes osteoblastic differentiation and improves fracture healing in mice

Maddison R. Johnstone, Rhys D. Brady, Johannes A. Schuijers, Jarrod E. Church, David Orr, Julian M.W. Quinn, Stuart J. McDonald, Brian L. Grills

Research output: Contribution to journalArticleResearchpeer-review

Abstract

OBJECTIVES: To study effects of the selective TrkA agonist, gambogic amide (GA), on fracture healing in mice and on an osteoprogenitor cell line in vitro. METHODS: Mice were given bilateral fibular fractures and treated for two weeks with vehicle or 1 mg/kg/day GA and euthanized at 14-, 21-, and 42-days post-fracture. Calluses were analysed by micro-computed tomography (µCT), three-point bending and histology. For RT-PCR analyses, Kusa O cells were treated with 0.5nM of GA or vehicle for 3, 7, and 14 days, while for mineralization assessment, cells were treated for 21 days. RESULTS: µCT analysis found that 21-day GA-treated calluses had both decreased tissue volume (p<0.05) and bone surface (p<0.05) and increased fractional bone volume (p<0.05) compared to controls. Biomechanical analyses of 42-day calluses revealed that GA treatment increased stiffness per unit area by 53% (p<0.01) and load per unit area by 52% (p<0.01). GA treatment increased Kusa O gene expression of alkaline phosphatase and osteocalcin (p<0.05) by 14 days as well as mineralization at 21 days (p<0.05). CONCLUSIONS: GA treatment appeared to have a beneficial effect on fracture healing at 21- and 42-days post-fracture. The exact mechanism is not yet understood but may involve increased osteoblastic differentiation and matrix mineralization.

Original languageEnglish
Pages (from-to)94-103
Number of pages10
JournalJournal of Musculoskeletal Neuronal Interactions
Volume19
Issue number1
Publication statusPublished - 1 Mar 2019

Cite this

Johnstone, M. R., Brady, R. D., Schuijers, J. A., Church, J. E., Orr, D., Quinn, J. M. W., ... Grills, B. L. (2019). The selective TrkA agonist, gambogic amide, promotes osteoblastic differentiation and improves fracture healing in mice. Journal of Musculoskeletal Neuronal Interactions, 19(1), 94-103.
Johnstone, Maddison R. ; Brady, Rhys D. ; Schuijers, Johannes A. ; Church, Jarrod E. ; Orr, David ; Quinn, Julian M.W. ; McDonald, Stuart J. ; Grills, Brian L. / The selective TrkA agonist, gambogic amide, promotes osteoblastic differentiation and improves fracture healing in mice. In: Journal of Musculoskeletal Neuronal Interactions. 2019 ; Vol. 19, No. 1. pp. 94-103.
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abstract = "OBJECTIVES: To study effects of the selective TrkA agonist, gambogic amide (GA), on fracture healing in mice and on an osteoprogenitor cell line in vitro. METHODS: Mice were given bilateral fibular fractures and treated for two weeks with vehicle or 1 mg/kg/day GA and euthanized at 14-, 21-, and 42-days post-fracture. Calluses were analysed by micro-computed tomography (µCT), three-point bending and histology. For RT-PCR analyses, Kusa O cells were treated with 0.5nM of GA or vehicle for 3, 7, and 14 days, while for mineralization assessment, cells were treated for 21 days. RESULTS: µCT analysis found that 21-day GA-treated calluses had both decreased tissue volume (p<0.05) and bone surface (p<0.05) and increased fractional bone volume (p<0.05) compared to controls. Biomechanical analyses of 42-day calluses revealed that GA treatment increased stiffness per unit area by 53{\%} (p<0.01) and load per unit area by 52{\%} (p<0.01). GA treatment increased Kusa O gene expression of alkaline phosphatase and osteocalcin (p<0.05) by 14 days as well as mineralization at 21 days (p<0.05). CONCLUSIONS: GA treatment appeared to have a beneficial effect on fracture healing at 21- and 42-days post-fracture. The exact mechanism is not yet understood but may involve increased osteoblastic differentiation and matrix mineralization.",
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The selective TrkA agonist, gambogic amide, promotes osteoblastic differentiation and improves fracture healing in mice. / Johnstone, Maddison R.; Brady, Rhys D.; Schuijers, Johannes A.; Church, Jarrod E.; Orr, David; Quinn, Julian M.W.; McDonald, Stuart J.; Grills, Brian L.

In: Journal of Musculoskeletal Neuronal Interactions, Vol. 19, No. 1, 01.03.2019, p. 94-103.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Johnstone, Maddison R.

AU - Brady, Rhys D.

AU - Schuijers, Johannes A.

AU - Church, Jarrod E.

AU - Orr, David

AU - Quinn, Julian M.W.

AU - McDonald, Stuart J.

AU - Grills, Brian L.

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N2 - OBJECTIVES: To study effects of the selective TrkA agonist, gambogic amide (GA), on fracture healing in mice and on an osteoprogenitor cell line in vitro. METHODS: Mice were given bilateral fibular fractures and treated for two weeks with vehicle or 1 mg/kg/day GA and euthanized at 14-, 21-, and 42-days post-fracture. Calluses were analysed by micro-computed tomography (µCT), three-point bending and histology. For RT-PCR analyses, Kusa O cells were treated with 0.5nM of GA or vehicle for 3, 7, and 14 days, while for mineralization assessment, cells were treated for 21 days. RESULTS: µCT analysis found that 21-day GA-treated calluses had both decreased tissue volume (p<0.05) and bone surface (p<0.05) and increased fractional bone volume (p<0.05) compared to controls. Biomechanical analyses of 42-day calluses revealed that GA treatment increased stiffness per unit area by 53% (p<0.01) and load per unit area by 52% (p<0.01). GA treatment increased Kusa O gene expression of alkaline phosphatase and osteocalcin (p<0.05) by 14 days as well as mineralization at 21 days (p<0.05). CONCLUSIONS: GA treatment appeared to have a beneficial effect on fracture healing at 21- and 42-days post-fracture. The exact mechanism is not yet understood but may involve increased osteoblastic differentiation and matrix mineralization.

AB - OBJECTIVES: To study effects of the selective TrkA agonist, gambogic amide (GA), on fracture healing in mice and on an osteoprogenitor cell line in vitro. METHODS: Mice were given bilateral fibular fractures and treated for two weeks with vehicle or 1 mg/kg/day GA and euthanized at 14-, 21-, and 42-days post-fracture. Calluses were analysed by micro-computed tomography (µCT), three-point bending and histology. For RT-PCR analyses, Kusa O cells were treated with 0.5nM of GA or vehicle for 3, 7, and 14 days, while for mineralization assessment, cells were treated for 21 days. RESULTS: µCT analysis found that 21-day GA-treated calluses had both decreased tissue volume (p<0.05) and bone surface (p<0.05) and increased fractional bone volume (p<0.05) compared to controls. Biomechanical analyses of 42-day calluses revealed that GA treatment increased stiffness per unit area by 53% (p<0.01) and load per unit area by 52% (p<0.01). GA treatment increased Kusa O gene expression of alkaline phosphatase and osteocalcin (p<0.05) by 14 days as well as mineralization at 21 days (p<0.05). CONCLUSIONS: GA treatment appeared to have a beneficial effect on fracture healing at 21- and 42-days post-fracture. The exact mechanism is not yet understood but may involve increased osteoblastic differentiation and matrix mineralization.

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