Novel chondrogenic and chondroprotective effects of the natural compound harmine

Abstract

A significant number of natural compounds have been shown to regulate the behavior of the cells, in collaboration with cellular proteins. CCN2/connective tissue growth factor (CTGF) has been reported to have essential roles in cartilage development, chondrocyte proliferation and differentiation as well as regulation of the extracellular matrix metabolism. Previous studies demonstrated the capability of CCN2 to regenerate surgical defects in articular cartilage of rat knee. Also, transgenic mice over-expressing cartilage-specific CCN2 were shown to be more resistant to aging-related cartilage degradation. We hypothesized that small molecules that induce CCN2 in chondrocytes could be novel candidates to increase the resistance to aging-related cartilage degradation, or even to correct cartilage degenerative changes incurred in OA. Therefore, this study screened a compound library and identified the β-carboline alkaloid harmine as a novel inducer of CCN2 in human chondrocytic HCS-2/8 cells and osteoarthritic articular chondrocytes. Harmine increased the expression of the cartilage markers aggrecan and COL2α1, as well as that of the master regulator of chondrogenesis, SOX-9. Moreover, harmine notably induced chondrogenesis of prechondrocytic ATDC5 cells in micromass cultures. The chondroprotective effect of harmine was investigated under inflammatory condition by stimulation with TNFα, and harmine was shown to ameliorate TNFα-induced decrease in expression of CCN2 and cartilage markers. These findings uncover novel chondrogenic effects of harmine and indicate harmine as a potential drug for prevention and/or repair of cartilage degradation.

A short-term treatment with tumor necrosis factor-alpha enhances stem cell phenotype of human dental pulp cells

“…DPCs were dissociated with accutase and filtered through a 70-μm cell strainer, washed, resuspended in phosphate-buffered saline (PBS) containing 1% FBS, and incubated with antibodies (anti-human SSEA-4, CD29, CD34, CD44, CD45, CD90, and CD146 antibody; BD Biosciences, San Jose, CA, USA) for 30 minutes on ice [15]. Cells were washed and subjected to flow cytometry (FCM) analysis by MACSQuant Analyzer (Miltenyi Biotec, Bergisch Gladbach, Germany) or Accuri™ C6 (BD Biosciences).…”

The effect of Elaeagnus angustifolia L. whole fruit and medulla powder on women with osteoarthritis of the knee: A randomized controlled clinical trial

“…Through these mechanisms these alkaloids exert anti-nociceptive effects [37]. Additionally, Hara et al have revealed the chondroprotective effect of these alkaloids and have suggested that these alkaloids could be useful compounds for relieving pain and preventing cartilage degradation through aging or OA [38].…”

Natural Compounds: Molecular Weapons against Leukemia’s

“…Many natural compounds have been studied in these last years because of they are able to affect not only cell differentiation of solid tumors as chondrogenesis [67] and neuronal cells [68], but also of bone marrow-derived hematopoietic cells. Although the main differentiation inducer in acute promyelocytic leukemia therapy has been all-trans retinoic acid (ATRA), these compounds can support traditional anticancer chemotherapies or enhance the effect of ATRA [69].…”