Decreased osteogenesis in mesenchymal stem cells derived from the aged mouse is associated with enhanced NF-κB activity

Tzu Hua Lin, Emmanuel Gibon, Florence Loi, Jukka Pajarinen, Luis A. Córdova, Akira Nabeshima, Laura Lu, Zhenyu Yao, Stuart B. Goodman

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Aging is associated with significant bone loss and delayed fracture healing. NF-κB activation is highly correlated with inflammatory-associated bone diseases including infection, wear particle exposure, and chronic inflammation during natural aging processes. The critical roles of NF-κB in both the pro-inflammatory response and osteoclast-mediated bone resorption have been well defined. However, the biological effects of NF-κB activation in mesenchymal stem cell (MSC)-mediated bone formation remain largely unknown. In the current study, bone marrow-MSCs were isolated from young (8 weeks old) and aged (72 weeks old) mice. NF-κB activity in MSCs at basal levels and under different biological conditions were determined by our recently established lentiviral vectorbased luciferase reporter assay. We found that NF-κB activity was increased in aged MSCs at basal levels or when exposed to low dose (10 or 100 ng/ml) lipopolysaccharide (LPS); this effect was not seen when the cells were exposed to higher dose (1 µg/ml) LPS. During osteogenesis, NF-κB activity was increased in aged MSCs at weeks 1 and 2, but showed no significant difference at week 3. Both Smurf2 and TAZ, the NF-κB target genes that regulate osteogenic differentiation, were increased in aged MSCs. In addition, the expression of RANKL was dramatically increased, and OPG was decreased in aged MSCs. Our findings suggest that targeting NF-κB activity in MSCs has the potential to modulate aging-associated bone loss, or enhance bone-healing in aged patients.

Original languageEnglish
Pages (from-to)281-288
Number of pages8
JournalJournal of Orthopaedic Research
Volume35
Issue number2
DOIs
Publication statusPublished - Feb 1 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine

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