Abstract: In one aspect, engineered hematopoietic stem cells comprising a heterologous expression cassette are provided. In some embodiments, the expression cassette comprises a promoter operably linked to a polynucleotide that encodes a 1?-hydroxylase protein, wherein the 1?-hydroxylase protein is human cytochrome P450 family 27 subfamily B member 1 (CYP27B1).

Abstract: In one aspect, anabolic agent fusion proteins and compositions comprising anabolic agent fusion proteins are provided. In some embodiments, the anabolic agent fusion protein comprises a platelet derived growth factor (PDGF) or a fibroblast growth factor (FGF) and an Asp-Ser-Ser tripeptide (DSS) repeat sequence. In another aspect, methods of promoting bone growth and methods of treating a fracture using anabolic agent fusion proteins and compositions comprising anabolic agent fusion proteins are provided.

Abstract: Methods are disclosed herein for increasing bone mass and strength or bone fracture healing in a subject. The methods include administering to the subject a therapeutically effective amount of multipotent stem cells, wherein each multipotent stem cell is transformed with a recombinant nucleic acid molecule comprising a heterologous promoter operably linked to a nucleic acid encoding platelet derived growth factor (PDGF) B, and wherein the multipotent stem cells express a sufficient amount of PDGFB to increase bone mass and strength or bone fracture healing. A lentiviral vector also is disclosed that includes a phosphoglycerate kinase-1 (PGK) promoter operably linked to a nucleic acid encoding PDGFB.

Abstract: Methods are disclosed herein for increasing bone mass and strength or bone fracture healing in a subject. The methods include administering to the subject a therapeutically effective amount of multipotent stem cells, wherein each multipotent stem cell is transformed with a recombinant nucleic acid molecule comprising a heterologous promoter operably linked to a nucleic acid encoding platelet derived growth factor (PDGF) B, and wherein the multipotent stem cells express a sufficient amount of PDGFB to increase bone mass and strength or bone fracture healing. A lentiviral vector also is disclosed that includes a phosphoglycerate kinase-1 (PGK) promoter operably linked to a nucleic acid encoding PDGFB.

Abstract: Vectors, such as retroviral vectors and transposon-based nonviral vectors, are disclosed herein that can be used to target transgene expression to the proliferating periosteal cells and cells in the marrow space after bone fracture. In one embodiment, these vectors include a human Cox-2 gene that is modified to improve mRNA stability and protein translation by truncating the 3? untranslated region (UTR). In addition, in some embodiments, the native translation signal is replaced with an optimized Kozak sequence. These vectors can be used alone or with vectors expressing BMP2/4, FGF-2, or LMP-1 gene to repair bone fractures and increase prostaglandin secretion. Methods for identifying agents that accelerate bone repair are also disclosed.

Abstract: Vectors, such as retroviral vectors and transposon-based nonviral vectors, are disclosed herein that can be used to target transgene expression to the proliferating periosteal cells and cells in the marrow space after bone fracture. In one embodiment, these vectors include a human Cox-2 gene that is modified to improve mRNA stability and protein translation by truncating the 3? untranslated region (UTR). In addition, in some embodiments, the native translation signal is replaced with an optimized Kozak sequence. These vectors can be used alone or with vectors expressing BMP2/4, FGF-2, or LMP-1 gene to repair bone fractures and increase prostaglandin secretion. Methods for identifying agents that accelerate bone repair are also disclosed.