Phytoestrogen (Daidzein) Promotes Chondrogenic Phenotype of Human Chondrocytes in 2D and 3D Culture Systems

Abstract

Clinical investigations have shown a significant relationship between osteoarthritis (OA) and estrogens levels in menopausal women. Therefore, treatment with exogenous estrogens has been shown to decrease the risk of OA. However, the effect estrogen has not been clearly demonstrated in the chondrocytes using phytoestrogens, which lack the specific side-effects of estrogens, may provide an alternative therapy. This study was designed to examine the possible effects of phytoestrogen (daidzein) on human chondrocyte phenotype and extracellular matrix formation. Phytoestrogens which lack the specific side-effects of estrogens may provide beneficial effect without causing hormone based side effect. Human chondrocytes cells were cultured in 2D (flask) and 3D (PCL-CA scaffold) systems. Daidzein cytotoxic effect was determined by MTT assay. Chondrocyte cellular content of glycosaminoglycans (GAGs), total collagen and chondrogenic gene expression were determined in both culture systems after treatment with daidzein. Daidzein showed time-dependent and dose-independent effects on chondrocyte bioactivity. The compound at low doses showed significant (p \ 0.05) increase in total collagen and GAGs production at similar levels in 2D and 3D culture environment. The mRNA levels of Collagen II and Sox9 were increased significantly (p \ 0.01) after the treatment while the upregulation in COMP expression was statistically insignificant (p [ 0.05). The expression levels of Fibronectin, Laminin and Integrin b1 were significantly increased especially in 3D culture system. This study was illustrated the potential positive effects of daidzein on maintenance of human chondrocyte phenotype and extracellular matrix formation suggesting an attractive and viable alternative therapy for OA. Keywords Phytoestrogens Á Human chondrocyte Á Extracellular matrix Á PCL-CA scaffold Á Osteoarthritis Abbreviations CTX-II C-terminal crosslinked telopeptide type II collagen CA Citric acid COMP Cartilage oligomeric matrix protein COX Cyclooxygenase DMEM Dulbecco's Modification of Eagle's Medium DMMB Dimethylmethylene blue & Thamil Selvee Ramasamy

Sex-dependent variation in cartilage adaptation: from degeneration to regeneration

“…Similarly, another phytoestrogen, daidzein, had anti-inflammatory and anti-oxidant effects in a rat OA model, especially when in combination with hyaluronic acid therapy [ 201 ]. In human chondrocytes, daidzein has had comparable results, having positive effects on ECM formation and pheotype regulation [ 202 ]. These studies demonstrate using phytoestrogen as a therapy method could be a promising approach to treat OA.…”

Patient‑reported health outcomes for severe knee osteoarthritis after conservative treatment with an intra‑articular cell‑free formulation for articular cartilage regeneration combined with usual medical care vs. usual medical care alone: A randomized controlled trial

“…Even though it has been proven that those acids promote differentiation into bone cells (15–18), their capacity to generate, on their own, a morphologic differentiation into cartilage cells is a topic of debate (19,20). However, when those acids are combined with other co-factors, they aid in the process of differentiation into chondrocytes (14,21–23). According to previous reports of in vitro trials on animal models and human patients (11,24), the combination of the compounds present in BIOF2 act in synergy to modify the intra-articular microenvironment and stimulate articular regeneration by producing molecular and morphologic alterations in synovial fluid cells and chondrocytes (11).…”

Association between phytoestrogens and osteoarthritis based on NHANES database

“…The relationship between phytoestrogens and osteoarthritis is currently less studied and the relationship between phytoestrogens and OA is not consistent across studies. the study of Shen CL et al concluded that genistein, among others, can be anti-arthritic, and Mahmod et al [35] found in an experimental study based on human chondrocytes that the phytoestrogen daidzein had a signi cant effect on the maintenance of human chondrocyte phenotype and extracellular matrix formation, Gundogdu et al [36] concluded that the phytoestrogen daidzein has anti-in ammatory and antioxidant effects in a rat model of OA, and Jia C et al found in an experimental study based on human articular cartilage that the phytoestrogen formononetin inhibited the induction of nuclear factor κB and AKT by IL-1β. κB and AKT activation and thus could be used as a potential drug for OA treatment [37].…”