Tendon ruptures are among the most common musculoskeletal disorders that occur in both sport injuries and age-related degenerations [1,2]. While substantial advances have been made in tendon repairs during the past decades, their clinical outcomes, especially for the intra synovial tendon ruptures, such as rotator cuff tears, remain highly variable [3]. The high re-rupture rate has been attributed to factors including old age, poor vascularization, chronicity of tears, as well as fatty degeneration [4]. Tendon attaches to bone via special-structured enthesis, which is composed of four transitional zones, i.e. fibrous tendon, unmineralized fibrocartilage, mineralized fibrocartilage, and bony attachment [5]. The healing of tendon rupture starts with an inflammatory phase, which spans over a few days, shifting to a proliferative phase, which is characterized by several weeks of synthetic activity of tenocytes with production of type III collagen. It is then followed by a remodeling phase, dominated by synthesis of type I collagen and realignment of extracellular matrix (ECM), which can last more than one year [6]. The repaired tendon tissue commonly appears scar-like and never completely regains the original structure or biomechanical properties it had prior to injury [7].

Accumulating laboratory results indicate that biological augmentation with the application of mesenchymal stem cells (MSCs), collagen-rich ECMs, as well as growth factors, has the potential to enhance tendon healing [8], [9], [10]. During these approaches, MSCs can be applied directly to the site of tendon injury or can be delivered on a suitable scaffold that functions as carrier matrix for growth factors. Among the tenogenic growth factors, the bone morphogenetic protein 12 (BMP-12), the human homologue of murine growth differentiation factor 7 (GDF-7), has been drawn particular attention. Unlike the classic BMP family proteins, which induce in vivo bone or cartilage formation, BMP-12 belong to a subfamily of BMPs which can stimulate the formation of tendon-/ ligament–like tissues in animal models [12]. Up to date, several studies have been published which substantiates the stimulating effect of BMP-12 on the expression of tenogenic markers in MSC cultures in vitro. However, whether BMP-12 affects other lineage differentiations has not been investigated, though this has been shown with other BMP´s [13]. Since the severity of fatty infiltration has important implications on tendon healing and the importance of pharmacomodulation on healing and restoration of tissue homeostasis has great clinical importance [33,34], we consider that investigation on the effect of BMP-12 on adipocyte differentiation is necessary.

In the present study, the murine BMP-12 analogue, GDF-7, was applied to the MSC-collagen matrix tenogenic model. The effect of this growth factor on tenocytic, osteoblastic, and adipocytic differentiation was evaluated.