The role of the ERK1/2 pathway as an alternative to the aging-diminished cyclic AMP pathway in calcitonin-mediated chondrogenesis in human nucleus pulposus

Wei Hong Chen, Rong Zeng, Wen Cheng Lo, Szu Yu Tina Chen, Tung-Iuan Lai, David F. Williams, Win Ping Deng

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Human disc degeneration initiated by aging in the central nucleus pulposus (hNP) is an irreversible process and the recovery has become seriously emerging. In this study, the related mechanisms of calcitonin on the regeneration of hNP and the effects of calcitonin on the age-related alterations were examined. The harvested hNP population was designated as YhNP (from young donor, age 50). Primary OhNP cells showed more hypertrophic phenotypes than YhNP. However, calcitonin (10-8-10-6 M) was able to induce the same chondrogenesis in both YhNP and OhNP by elevating chondrogenic specific-mRNA and protein expressions. Their cell viabilities were increased with calcitonin treatment. No significant differences of calcitonin receptor (CTR) were expressed between YhNP and OhNP cells. Interestingly, in calcitonin-induced pathways for chondrogenesis, highly increased cyclic AMP (cAMP) was detected in YhNP but was strongly diminished by aging in OhNP after calcitonin treatment. However, to maintain the chondrogenesis, calcitonin-induced an alterative phosphorylated ERK1/2 (p-ERK) in both cells. After inhibiting ERK1/2 by PD98059, calcitonin-induced chondrogenesis in OhNP was almost restrained while YhNP cells were not affected. Our results demonstrated that the regeneration of calcitonin on hNP was maintained with aging which was satisfied by an alternative signaling pathway. Therefore, calcitonin shows great potential for clinical therapy for disc regeneration without aging considerations.

Original languageEnglish
Pages (from-to)8256-8264
Number of pages9
JournalBiomaterials
Volume33
Issue number33
DOIs
Publication statusPublished - Nov 2012

    Fingerprint

Keywords

  • Calcitonin
  • Disc degeneration
  • Disc regeneration
  • ERK1/2
  • Nucleus pulposus

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this