harmine and Osteoarthritis

Harmine, a β-carboline alkaloid, is widely distributed in the plants, animals as well as in human tissues and body fluids. Harmine has various types of pharmacological activities including antimicrobial, antiplasmodial, antioxidative, antitumor, antimutagenic, antidiabetic, vasorelaxant and central excitation properties. Moreover, it can exert regenerative and protective effects on bone and cartilage tissues by regulating the proliferation, differentiation and metabolism of osteoclasts, osteoblasts and chondrocytes. These features make harmine a novel candidate for the prevention and treatment of bone and cartilage diseases, such as osteoporosis, bone fracture and osteoarthritis.. 去氢骆驼蓬碱是一种β-咔啉类生物碱，广泛分布于植物、动物以及人体组织和体液中。它具有多种药理作用，包括抗菌、抗疟原虫、抗氧化、抗肿瘤、抗诱变、抗糖尿病、舒张血管和兴奋中枢等功能。此外，去氢骆驼蓬碱还可通过影响破骨细胞、成骨细胞和软骨细胞的增殖分化调控骨与软骨组织的形成和代谢，发挥对骨及软骨组织的促再生和保护作用，从而为骨质疏松、骨折及骨关节炎等疾病的防治开辟一条新途径。.

Topics: Bone and Bones; Cartilage; Cell Differentiation; Chondrocytes; Harmine; Humans; Osteoarthritis; Osteoblasts

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.

Topics: Aggrecans; Aging; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; Cartilage, Articular; Cell Differentiation; Cells, Cultured; Chondrocytes; Chondrogenesis; Collagen Type II; Connective Tissue Growth Factor; Extracellular Matrix; Gene Expression; Harmine; Humans; Osteoarthritis; Protective Agents; Small Molecule Libraries; SOX9 Transcription Factor; Tumor Necrosis Factor-alpha