期刊
JOURNAL OF MOLECULAR NEUROSCIENCE
卷 71, 期 8, 页码 1543-1555出版社
HUMANA PRESS INC
DOI: 10.1007/s12031-019-01448-z
关键词
PACAP; BMP; Collagen type I; ALP; Tibia fracture; Callus
资金
- University of Debrecen (DE)
- PTE AOK Research Grant [MTA-TKI 14016, GINOP-2.3.2-15-2016-00050]
- New National Excellence Program of the Ministry of Human Capacities [UNKP-16-4-IV]
- Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pecs [EFOP-3.6.1.-16-2016-00004]
- University of Debrecen (OTKA Bridging Fund) [EFOP-3.6.3-VEKOP-16-2017-00009]
- Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pecs (Budapest, Hungary) [EFOP-3.6.1.-16-2016-00004, NAP B KTIA NAP 13-2014-0022, 888819, NAP 2017-1.2.1-NKP-2017-00002, OTKA-NN 114458]
- Thematic Excellence Programme of the Ministry for Innovation and Technology in Hungary within University of Debrecen [ED 18-1-2019-0028]
- European Union
- European Social Fund
- Hungarian Academy of Science
- State of Hungary
- European Social Funding
- TAMOP 4.2.4
- The role of neuro-inflammation in neurodegeneration: from molecules to clinics Centre for Neuroscience of the University of Pecs [EFOP-3.6.2-16-2017-00008]
- Bolyai Janos Research Scholarship
- National Excellence Program [A/2-11-1-2012-0001]
- [NKFIK115874]
- [PD109644]
- [K119759]
- [NKFIHFK129190]
Research shows that PACAP plays important regulatory roles in central nervous system differentiation and chondrogenesis, as well as in bone remodeling and regeneration. In PACAP KO mice, ALP activation during healing process remains unaffected, but collagen type I expression decreases and BMP signaling elements are disrupted.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a naturally secreted signaling peptide and has important regulatory roles in the differentiation of the central nervous system and its absence results in disorders in femur development. PACAP has an important function in prevention of oxidative stress or mechanical stress in chondrogenesis but little is known about its function in bone regeneration. A new callus formation model was set to investigate its role in bone remodeling. Fracturing was 5 mm distal from the proximal articular surface of the tibia and the depth was 0.5 mm. Reproducibility of callus formation was investigated with CT 3, 7, and 21 days after the operation. Absence of PACAP did not alter the alkaline phosphatase (ALP) activation in PACAP KO healing process. In developing callus, the expression of collagen type I increased in wild-type (WT) and PACAP KO mice decreased to the end of healing process. Expression of the elements of BMP signaling was disturbed in the callus formation of PACAP KO mice, as bone morphogenic protein 4 (BMP4) and 6 showed an early reduction in bone regeneration. However, elevated Smad1 expression was demonstrated in PACAP KO mice. Our results indicate that PACAP KO mice show various signs of disturbed bone healing and suggest PACAP compensatory and fine tuning effects in proper bone regeneration.
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