Pituitary adenylate cyclase activating polypeptide (PACAP) reduces oxidative and mechanical stress-evoked matrix degradation in chondrifying cell cultures

Eszter Szentléleky, Vince Szegeczki, Edina Karanyicz, Tibor Hajdú, A. Tamás, G. Tóth, Róza Zákány, D. Reglodi, Tamás Juhász

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide also secreted by non-neural cells, including chondrocytes. PACAP signaling is involved in the regulation of chondrogenesis, but little is known about its connection to matrix turnover during cartilage formation and under cellular stress in developing cartilage. We found that the expression and activity of hyaluronidases (Hyals), matrix metalloproteinases (MMP), and aggrecanase were permanent during the course of chondrogenesis in primary chicken micromass cell cultures, although protein levels changed daily, along with moderate and relatively constant enzymatic activity. Next, we investigated whether PACAP influences matrix destructing enzyme activity during oxidative and mechanical stress in chondrogenic cells. Exogenous PACAP lowered Hyals and aggrecanase expression and activity during cellular stress. Expression and activation of the majority of cartilage matrix specific MMPs such as MMP1, MMP7, MMP8, and MMP13, were also decreased by PACAP addition upon oxidative and mechanical stress, while the activity of MMP9 seemed not to be influenced by the neuropeptide. These results suggest that application of PACAP can help to preserve the integrity of the newly synthetized cartilage matrix via signaling mechanisms, which ultimately inhibit the activity of matrix destroying enzymes under cellular stress. It implies the prospect that application of PACAP can ameliorate articular cartilage destruction in joint diseases.

Original languageEnglish
Article number168
JournalInternational Journal of Molecular Sciences
Volume20
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

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Pituitary Adenylate Cyclase-Activating Polypeptide
Mechanical Stress
polypeptides
Cell culture
cartilage
Oxidative Stress
Cartilage
Cell Culture Techniques
degradation
Degradation
matrices
Chondrogenesis
Hyaluronoglucosaminidase
Neuropeptides
Matrix Metalloproteinases
chickens
enzyme activity
Joint Diseases
Enzyme activity
Articular Cartilage

Keywords

  • Aggrecanase
  • Hyaluronidase
  • Matrix metalloproteinase
  • Mechanical stress
  • Oxidative stress

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Pituitary adenylate cyclase activating polypeptide (PACAP) reduces oxidative and mechanical stress-evoked matrix degradation in chondrifying cell cultures. / Szentléleky, Eszter; Szegeczki, Vince; Karanyicz, Edina; Hajdú, Tibor; Tamás, A.; Tóth, G.; Zákány, Róza; Reglodi, D.; Juhász, Tamás.

In: International Journal of Molecular Sciences, Vol. 20, No. 1, 168, 01.01.2019.

Research output: Contribution to journalArticle

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