While both induction culture matrix and media have already been reported to modify the stem cell fate, little is well known about which factor takes on a far more decisive part in directing the MSC differentiation lineage aswell as the underlying mechanisms. profound effect on directing the differentiation lineage than the induction media did. The strong modulation effect on the transcription activities might be the critical factor contributing to the above observations in our study, where canonical Wnt–Catenin signal pathway was directly involved in the matrix-driven osteoblastic differentiation. Such findings not only provide a critical insight on natural cellular events leading to the osteoblastic and chondrocytic differentiations, but also have important implications in biomaterial design for tissue engineering applications. manipulations. A critical component of the stem cell niche is its residing matrix, and numerous studied have reported that the matrix exert a profound effect on various MSC functions, including attachment, proliferation, migration and differentiation [6, 19]. For instance, selecting the extracellular matrix (ECM) or ECM-derived materials has been trusted in modulating and stimulating MSC features [6, 20]. Even more interestingly, it’s been reported how the matrix itself might exert a crucial rules influence on MSC fate decision. Our previous research revealed that collection of collagen rather than synthesized hydrogel together with the hydroxyapatite activated the MSC differentiation in to the osteoblastic lineage, that will be related to the accelerated MSC condensation and solid cell-cell and cell-matrix interactions [21]. Certainly, the ECM offers a beneficial microenvironment for different cellular responses, such as for example survival, differentiation and migration, by advertising adhesion, modulating the actions of growth reasons and cytokines and activating intracellular signaling [21] directly. Besides, surface area function organizations exert solid impact for the stem cell lineage standards also, though modulating the framework and molecular structure of cell-matrix adhesions [22C25]. Furthermore, the matrix varies not merely in chemical structure, however in physical properties also, like the topography and elasticity. Such physical properties would also impact a variety of cellular procedures through adjustments in focal adhesion as well as the actin cytoskeleton [26, 27]. For instance, Engler demonstrated that matrix elasticity can designate stem cell lineage toward neurons, osteoblasts and myoblasts, indicating a GNAQ crucial part of physical environment on MSC fate decisions [28]. In a nutshell, earlier studies show that both induction culture matrix and media could regulate stem cell fate. However, which element takes on a more decisive role in directing the MSC differentiation lineage, and the underlying mechanisms for both regulating effect remain to be elucidated. For instance, the osteogenic-based HA-collagen matrix seems have a strong influence around the transcriptional factor Runx2, but would that be the main mechanism and how would the matrix affect the transcriptional activities? On the other hand, whether the osteogenic induction media (Dex) affect the transcriptional activity or not remains controversial [11]. AP24534 distributor It is also of great interest to understand the potential correlating role of both factors for clinical applications in bone and cartilage repair. To address the above questions is usually of great importance for tissue engineering applications. For the treatment of osteochondral damage, it is desirable to design new biomaterial scaffolds offering different and sufficient circumstances for guiding the development of both cartilage and subchondral bone tissue, satisfying their different useful and natural requirements [29, 30]. Different techniques have already been followed for cartilage and bone tissue regenerations, utilizing the induction matrix and mass AP24534 distributor media selection, or the mix of both. For instance, Mikos possess utilized the same injectable and biodegradable hydrogel to fabricate a bi-layered osteochondral build through the use of different growth elements or induction mass media to market the MSC differentiation in to the respective lineages [31]. Chen and co-workers possess designed a book layered osteochondral scaffold consisting of the upper collagen layer and the lower collagen/HA layer to simultaneously drive the chondrogenic and osteogenic differentiations, respectively [32]. Nevertheless, they were insufficient in driving the lineage commitment and still required induction media to accelerate the osteogenesis [31, 32]. It is important to understand the underlying mechanisms of how both factors impact the osteogenesis and chondrogenesis. The current study aimed to address the above question by performing a parallel comparison between induction media and matrix AP24534 distributor in terms of their capabilities to modulate the MSC fate into the osteoblastic and chondrocytic lineage. We selected two matrixes: HA-collagen and HA-synthetic hydrogel, which experienced showed highly different potentials toward osteoblastic and chondrocytic differentiation lineages, respectively [21]. The MSCs were seeded around the above two matrix surfaces, and cultured under three different culture media, i.e. the normal culture medium, osteogenic induction medium, and chondrogenic induction medium, respectively. The effects of both matrix.