Osteoarthritis: A complicated joint disease requiring extensive studies with multiple approaches.

Osteoarthritis (OA) is an aging-related degenerative joint disease caused by alterations of local joint mechanical loading leading to the changes in one or more signaling pathways initiated from synovial tissue or articular cartilage [1]. OA often occurs at knee joint, hip joint, temporomandibular joint and facet joint [[1], [11]]. It has been shown that multiple signaling pathways or signaling molecules are involved in OA development [[1], [2], [3]]. Although it is not totally clear which types of joint tissue is involved in OA initiation, the recent longitudinal studies suggest that early molecular and morphological changes start from synovial tissue, followed by the alterations of articular cartilage and subchondral bone. Osteophyte formation is the later event of OA development [4]. The pathological mechanisms of OA are currently unknown. Recent studies suggest that vascular invasion and nerve ingrowth in articular cartilage may be responsible for OA development in a subgroup of OA patients [5,6]. The repairment of cartilage defects caused by OA or other pathological reasons has been extensively studied in recent years and multiple approaches have been applied for this purpose. Among these approaches, cell-based therapies seem more promising and attractive. Mesenchymal stromal cells (MSCs) have been demonstrated to help cartilage regeneration. These cells are often delivered by carriers, such as hydrogels or nanomaterials or through 3D printing technique [[7], [8], [9], [10]]. MSCs are able to differentiate into chondrocyte-like cells with the help of addition of growth factors, such as TGF-β3; however, more effective approach could be further developed by prevention of MSC-derived chondrocytes going to the process of hypertrophy resulting in cartilage calcification.