1.Bone Morphogenetic Proteins Bone morphogenetic proteins (BMPs) were originally isolated in the search for the regenerative molecules within bone matrix.BMPs form a single family of cystine-knot cytokines, sharing the characteristic fold of the transforming growth factor-beta superfamily.BMPs primarily function by causing the proliferation and differentiation of mesenchymal stem cells or chondro-/osteo-progenitor cells involved in endochondral or intramembranous ossification.Besides the ability to induce bone formation which gave BMPs their name, BMPs display morphogenetic activities in the development of a wide range of tissues.BMPs interact with combinations of type Ⅰ and type Ⅱ receptor dimers to produce multiple possible signalling complexes, leading to the activation of one of two competing sets of Smad transcription factors.BMPs have highly specific and localized functions.These are regulated in a number of ways, including the developmental restriction of BMP expression and through the secretion of several specific BMP antagonist proteins that bind with high affinity to BMPs.2.Application of BMPs to Enhancement of Fracture Healing BMPs have been studied widely to apply them to enhancement of fracture healing.The author have conducted several studies.Firstly, the author and colleagues reported the effectiveness of recombinant human BMP-7 to prevent nonunion formation and repair a rat nonunion model.BMP-7 is one of the BMP members and possesses strong osteogenic activity.The rat nonunion model was produced by the cauterization of periosteum which is important in fracture healing.Aging is a risk factor of delaying fracture healing, however, we demonstrated that rhBMP-7 effectively acted both in young and old rats.Nonunion is a challenging problem that may occur following certain bone fractures,however, there has been little investigation of the molecular basis of nonunions.We investigate and compare the gene expression patterns of BMPs and their antagonists in standard healing fractures and nonunions using rat experimental models.Gene expression of BMP-2, 3, 3B, 4, 6, 7, GDF-5, 7, and BMP antagonists noggin, drm, screlostin, and BAMBI were significantly lower in nonunions compared to standard healing fractures at several time points.The results of our study suggested that downregulation in expression of osteogenic BMPs might account for the nonunions of fracture and the balance between BMPs and their endogenous antagonists was critical for optimal fracture healing.Additionally, we reported that cells derived from human fracture nonunion tissue responded to rhBMP-7 and the osteogenic differentiation of them was induced.Recombinant human BMP-2 and 7 have already been clinically used,however the success rate of healing is not perfect.Further research is needed to improve the effective use of BMPs.