Genetics Institute, Inc.

Harvard College

Other

Signal Pharmaceuticals, Inc.

Genetics, Institute Institute, Llc.

Gerald H Thomsen

John Martin Wozney

Douglas A Melton

Neil M Wolfman

Anthony J Celeste

Vicki A Rosen

Jeffrey Wrana

Compositions of proteins with tendon/ligament-like tissue inducing activity are disclosed. The compositions are useful in the treatment of tendinitis and tendon or ligament defects and in related tissue repair.

Tendon-inducing methods

This invention provides unique members of the Hect family of ubiquitin ligases that specifically target BMP and TGF&#x3b2;/activin pathway-specific Smads. The novel ligases have been named Smurf1 and Smurf2. They directly interact with Smads1 and 5 and Smad7, respectively, and regulate the ubiquitination, turnover and activity of Smads and other proteins of these pathways. Smurf1 interferes with biological responses to BMP, but not activin signaling. In amphibian embryos Smurf1 inhibits endogenous BMP signals, resulting in altered pattern formation and cell fate specification in the mesoderm and ectoderm. The present invention provides a unique regulatory link between the ubiquitination pathway and the control of cell fate determination by the TGF&#x3b2; superfamily during embryonic development. Thus, Smurf1 is a negative regulator of Smad1 signal transduction, by targeting Smad1, Smurf1 blocks BMP signaling. In mammalian cells, Smurf2 suppresses TGF&#x3b2; signalling, and in, blocks formation of dorsal mesoderm and causes anterior truncation of the embryos. Smurf2 forms a stable complex with Smad7, which induces degradation and downregulation of TGF&#x3b2;/activin signalling.

Modulators of Smurf and BMP/TGF&#x3b2; signaling pathways

Tendon-inducing compositions

The present invention relates to a novel family of purified proteins, and compositions containing such proteins, which compositions are useful for the induction of tendon/ligament-like tissue formation, wound healing and ligament and other tissue repair. The present invention further relates to DNA molecules, vectors and host cells useful for production of such proteins.

BMP-12 and BMP-13 proteins and DNA encoding them

The present invention relates to methods for the induction of tendon/ligament-like tissue formation, wound healing and ligament and other tissue repair, using a composition comprising BMP-12, BMP-13 or MP-52, or combinations of the above.

Methods of inducting formation of tendon and/or ligament tissue

Growing community of inventors

Port Jefferson, NY, United States of America

Gerald H Thomsen