Parathyroid hormone stimulates bone regeneration in an atrophic non-union model in aged mice.
Aging
Angiogenesis
Bone regeneration
Fracture healing
Inflammation
Mice
Non-union
Parathyroid hormone
Segmental defect
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
23 Nov 2023
23 Nov 2023
Historique:
received:
21
08
2023
accepted:
26
10
2023
medline:
27
11
2023
pubmed:
24
11
2023
entrez:
23
11
2023
Statut:
epublish
Résumé
Non-union formation still represents a major burden in trauma and orthopedic surgery. Moreover, aged patients are at an increased risk for bone healing failure. Parathyroid hormone (PTH) has been shown to accelerate fracture healing in young adult animals. However, there is no information whether PTH also stimulates bone regeneration in atrophic non-unions in the aged. Therefore, the aim of the present study was to analyze the effect of PTH on bone regeneration in an atrophic non-union model in aged CD-1 mice. After creation of a 1.8 mm segmental defect, mice femora were stabilized by pin-clip fixation. The animals were treated daily with either 200 mg/kg body weight PTH 1-34 (n = 17) or saline (control; n = 17) subcutaneously. Bone regeneration was analyzed by means of X-ray, biomechanics, micro-computed tomography (µCT) imaging as well as histological, immunohistochemical and Western blot analyses. In PTH-treated animals bone formation was markedly improved when compared to controls. This was associated with an increased bending stiffness as well as a higher number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD31-positive microvessels within the callus tissue. Furthermore, PTH-treated aged animals showed a decreased inflammatory response, characterized by a lower number of MPO-positive granulocytes and CD68-positive macrophages within the bone defects when compared to controls. Additional Western blot analyses demonstrated a significantly higher expression of cyclooxygenase (COX)-2 and phosphoinositide 3-kinase (PI3K) in PTH-treated mice. Taken together, these findings indicate that PTH is an effective pharmacological compound for the treatment of non-union formation in aged animals.
Sections du résumé
BACKGROUND
BACKGROUND
Non-union formation still represents a major burden in trauma and orthopedic surgery. Moreover, aged patients are at an increased risk for bone healing failure. Parathyroid hormone (PTH) has been shown to accelerate fracture healing in young adult animals. However, there is no information whether PTH also stimulates bone regeneration in atrophic non-unions in the aged. Therefore, the aim of the present study was to analyze the effect of PTH on bone regeneration in an atrophic non-union model in aged CD-1 mice.
METHODS
METHODS
After creation of a 1.8 mm segmental defect, mice femora were stabilized by pin-clip fixation. The animals were treated daily with either 200 mg/kg body weight PTH 1-34 (n = 17) or saline (control; n = 17) subcutaneously. Bone regeneration was analyzed by means of X-ray, biomechanics, micro-computed tomography (µCT) imaging as well as histological, immunohistochemical and Western blot analyses.
RESULTS
RESULTS
In PTH-treated animals bone formation was markedly improved when compared to controls. This was associated with an increased bending stiffness as well as a higher number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD31-positive microvessels within the callus tissue. Furthermore, PTH-treated aged animals showed a decreased inflammatory response, characterized by a lower number of MPO-positive granulocytes and CD68-positive macrophages within the bone defects when compared to controls. Additional Western blot analyses demonstrated a significantly higher expression of cyclooxygenase (COX)-2 and phosphoinositide 3-kinase (PI3K) in PTH-treated mice.
CONCLUSION
CONCLUSIONS
Taken together, these findings indicate that PTH is an effective pharmacological compound for the treatment of non-union formation in aged animals.
Identifiants
pubmed: 37996876
doi: 10.1186/s12967-023-04661-y
pii: 10.1186/s12967-023-04661-y
pmc: PMC10668449
doi:
Substances chimiques
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Parathyroid Hormone
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
844Informations de copyright
© 2023. The Author(s).
Références
J Orthop Res. 2005 Nov;23(6):1300-7
pubmed: 15936915
Bone. 2008 Dec;43(6):1075-83
pubmed: 18773980
Indian J Orthop. 2009 Apr;43(2):117-20
pubmed: 19838359
J Orthop Res. 2009 Sep;27(9):1152-6
pubmed: 19215028
J Bone Joint Surg Am. 2006 Nov;88 Suppl 3:140-7
pubmed: 17079380
J Orthop Res. 2018 Oct;36(10):2586-2594
pubmed: 29926970
Int J Mol Sci. 2019 Nov 02;20(21):
pubmed: 31684035
Bone. 2009 Feb;44(2):335-44
pubmed: 19013264
Methods Mol Biol. 2014;1130:149-164
pubmed: 24482171
J Orthop Trauma. 1996;10(4):279-84
pubmed: 8723407
J Endocrinol. 2011 Nov;211(2):123-30
pubmed: 21673026
Bone. 2005 Apr;36(4):678-87
pubmed: 15781006
J Orthop Traumatol. 2019 Apr 11;20(1):21
pubmed: 30976944
J Bone Joint Surg Am. 2004 Jul;86(7):1359-65
pubmed: 15252081
J Surg Res. 2008 Jun 1;147(1):84-91
pubmed: 18061614
Tissue Eng Part B Rev. 2021 Apr;27(2):107-132
pubmed: 32635857
Tissue Eng Part A. 2009 Sep;15(9):2637-42
pubmed: 19207046
J Bone Miner Res. 2005 Jul;20(7):1114-24
pubmed: 15940364
Calcif Tissue Int. 2012 Jun;90(6):507-14
pubmed: 22527206
J Bone Miner Res. 2009 Feb;24(2):251-64
pubmed: 18847332
Acta Orthop. 2013 Feb;84(1):106-11
pubmed: 23409846
J Craniofac Surg. 2004 May;15(3):424-7; discussion 428-9
pubmed: 15111801
J Orthop Res. 2019 Jan;37(1):35-50
pubmed: 30370699
J Bone Joint Surg Br. 2007 Dec;89(12):1553-60
pubmed: 18057352
Science. 2002 May 31;296(5573):1655-7
pubmed: 12040186
J Gerontol A Biol Sci Med Sci. 2022 May 5;77(5):909-917
pubmed: 34626193
J Surg Res. 2017 Dec;220:327-335
pubmed: 29180199
J Bone Miner Res. 2005 Nov;20(11):2017-27
pubmed: 16234975
Injury. 2014 Jun;45 Suppl 2:S8-S15
pubmed: 24857030
Curr Osteoporos Rep. 2018 Apr;16(2):155-168
pubmed: 29536393
Eur Cell Mater. 2013 Jul 16;26:1-12; discussion 12-4
pubmed: 23857280
Injury. 2008 Sep;39 Suppl 2:S45-57
pubmed: 18804573
Nat Rev Rheumatol. 2015 Jan;11(1):45-54
pubmed: 25266456
J Natl Cancer Inst. 1975 Jul;55(1):37-45
pubmed: 169366
J Bone Miner Res. 1996 May;11(5):568-77
pubmed: 9157771
Curr Osteoporos Rep. 2017 Dec;15(6):601-608
pubmed: 29143915
Bioengineering (Basel). 2023 Feb 20;10(2):
pubmed: 36829769
Eur Cell Mater. 2011 Jul 06;22:1-11
pubmed: 21732278
Clin Orthop Relat Res. 2007 May;458:175-9
pubmed: 17224836
Injury. 2014 Jun;45 Suppl 2:S3-7
pubmed: 24857025
Aging Cell. 2020 Mar;19(3):e13112
pubmed: 32096907
J Bone Miner Res. 2005 Oct;20(10):1715-22
pubmed: 16160729
J Anat. 1990 Aug;171:233-9
pubmed: 2081707
Exp Gerontol. 2006 Nov;41(11):1080-93
pubmed: 17092679
Injury. 2009 Dec;40 Suppl 3:S4-7
pubmed: 20082790
Endocrinology. 1986 Feb;118(2):824-8
pubmed: 3455914
Bone. 2016 May;86:119-30
pubmed: 26946132
J Orthop Trauma. 1989;3(2):142-7
pubmed: 2738762
Ann N Y Acad Sci. 2000 Jun;908:244-54
pubmed: 10911963
J Bone Miner Res. 1999 Jun;14(6):960-8
pubmed: 10352105
J Bone Joint Surg Am. 2012 Jan 4;94(1):49-58
pubmed: 22218382
Bone. 2017 Feb;95:124-135
pubmed: 27884787
HSS J. 2010 Feb;6(1):85-94
pubmed: 19763695
J Orthop Res. 1985;3(4):389-404
pubmed: 3906062
Res Pract Thromb Haemost. 2019 Nov 02;4(1):86-91
pubmed: 31989088