Current Pharmaceutical Design - Volume 19, Issue 19, 2013

There remains a great need to develop therapeutic agents to treat critical size defects and non-union fractures and one of the potential agents is recombinant human fibroblast growth factor 2 (FGF-2). We discuss the function of FGF-2 in bone formation, bone resorption, and downstream signaling pathways and review the role of exogenous FGF-2 in fracture healing. The importance of endogenous FGF-2 in bone formation Read More

Growth differentiation factor 5 (GDF5) is a member of the bone morphogenic protein (BMP) family and plays critical roles in organ development processes including bone, cartilage, ligament, and joint formation. GDF5 is expressed in the cartilage primordium in the early limb development, and in the interzone of joint formation sites. GDF5 is also observed in adult tissue and cell lines. This spatialtemporal expression pattern Read More

Both osteogenesis and angiogenesis are integrated parts of bone growth and regeneration. Combined delivery of osteogenic and angiogenic factors is a novel approach in bone regenerative engineering. Exogenous addition of mesenchymal stem cells (MSCs), vascular endothelial growth factor (VEGF) and bone morphogenetic proteins (BMPs) together with an osteoconductive scaffold is a very promising method to enhanc Read More

Recombinant human PDGF BB homodimer (rhPDGF-BB) is a potent recruiter of, and strong mitogenic factor for, cells crucial to musculoskeletal tissue repair, including mesenchymal stem cells (MSCs), osteogenic cells and tenocytes. rhPDGF-BB also upregulates angiogenesis. These properties allow rhPDGF-BB to trigger the cascade of bone and adjoining soft tissue repair and regeneration. This mechanism of action h Read More

Due to their short half-life and diffusion away from the site of regeneration, osteogenic proteins, used in regenerative medicine, require high doses leading to undesirable side effects. An exciting approach is to utilize peptides derived from the active domains of soluble and insoluble components of the bone extracellular matrix (ECM) to initiate the cascade of osteogenesis, vasculogenesis, mineralization, and bone formation. Oste Read More

Regeneration of bone requires the coordinated processes of angiogenesis and osteogenesis. These repair mechanisms are closely linked through both direct cell-cell contact and indirect paracrine signaling among osteoblasts, endothelial cells, and other cell types. The vasculature provides a source of nutrients, oxygen, metabolic substrates, and access for circulating cells that help to support new bone formation. The comple Read More

Tissue engineering aims to repair, restore, and regenerate lost or damaged tissues by using biomaterials, cells, mechanical forces and factors (chemical and biological) alone or in combination. Growth factors are routinely used in the tissue engineering approach to expedite the process of regeneration. The growth factor approach has been hampered by several complications including high dose requirements, lower half-lif Read More

The field of regenerative medicine and tissue engineering is an ever evolving field that holds promise in treating numerous musculoskeletal diseases and injuries. An important impetus in the development of the field was the discovery and implementation of stem cells. The utilization of mesenchymal stem cells, and later embryonic and induced pluripotent stem cells, opens new arenas for tissue engineering and presents Read More

Worldwide, more than 2.2 million patients undergo bone graft procedures annually. In each of these procedures an interface is formed between the host tissue and the graft material. Synthetic implants exhibit an interface with the host tissue and the formation of a homogenous interface consisting of bone and void of intervening soft tissue is desired (osseointegration); recent developments have highlighted the benefit of i Read More

There is a profound need for orthopaedic grafting strategies due to various trauma and musculoskeletal diseases. Tissue engineering offers a promising avenue to develop viable grafts for bone repair. The transfer of bone tissue engineering strategies to clinical applications is limited by the failure to adequately vascularize scaffolds after implantation. This review focuses on the natural processes for bone and vessel formatio Read More

Nonunions and delayed unions are among the more challenging clinical and surgical entities an orthopaedic surgeon must manage. Effective strategies that address these complex problems are in need and gene therapy represents a potential therapeutic option. Among the many properties that bone morphogenetic proteins (BMPs) possess, their potent osteoinductive effects make them attractive growth factors fo Read More

Cystic fibrosis (CF) is a common inherited fatal disease affecting 70,000 people worldwide, with a median predicted age of survival of approximately 38 years. The deletion of Phenylalanine in position 508 of the Cystic Fibrosis Transmembrane conductance Regulator (F508del-CFTR) is the most common mutation in CF patients: the deleted protein, not properly folded, is degraded. To date no commercial drugs are available. Low Read More

Correcting multiple defects of mutant CFTR with small molecule compounds has been the goal of an increasing number of recent Cystic Fibrosis (CF) drug discovery programmes. However, the mechanism of action (MoA) by which these molecules restore mutant CFTR is still poorly understood, in particular of CFTR correctors, i.e., compounds rescuing to the cells surface the most prevalent mutant in CF patients - F5 Read More

Cystic fibrosis (CF) is a multisystem disease associated with mutations in the gene that encodes the CF transmembrane conductance regulatory (CFTR) protein. The majority of wild-type CFTR and virtually all mutant ΔF508 CFTR are degraded before reaching the cell surface. Certain agents and conditions that increase expression and maturation of CFTR enable the protein to function at the cell surface. We and several resea Read More

Genistein and curcumin are major components of Asian foods, soybean and curry turmeric respectively. These compounds have been intensively investigated for their chemical and biological features conferring their anti-cancer activity. Genistein and curcumin have also been investigated for their potentiation effects on disease-associated CFTR mutants such as ΔF508 and G551D. Recently, we investigated the combined effect Read More

The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a cAMP-regulated Cl- channel whose major function is to facilitate epithelial fluid secretion. Loss-of-function mutations in CFTR cause the genetic disease cystic fibrosis. CFTR is required for transepithelial fluid transport in certain secretory diarrheas, such as cholera, and for cyst expansion in autosomal dominant polycystic kidney disease. High- Read More