Abstract: This invention is based, at least in part, on the discovery that Shn2 and Shn3 play an important role in skeletal remodeling and skeletal patterning. Accordingly, the present invention provides methods for identifying medulators of Shn2 activity and methods for modulating bone formation and mineralization and Shn2-associated disorders using agents that modulate Shn2 expression and/or activity, in addition to methods for modulating Shn2 and Shn3.

Abstract: This invention is based, at least in part, on the discovery that Shn2 and Shn3 play an important role in skeletal remodeling and skeletal patterning. Accordingly, the present invention provides methods for identifying medulators of Shn2 activity and methods for modulating bone formation and mineralization and Shn2-associated disorders using agents that modulate Shn2 expression and/or activity, in addition to methods for modulating Shn2 and Shn3.

Abstract: The present invention is based, at least in part, on the identification of molecules involved in the differentiation and/or activity of osteoblasts and osteoclasts. Accordingly, the present invention provides methods of identifying modulators of bone formation, mineralization, and/or osteoclastogenesis and methods for treating disorders that would benefit from modulation of bone formation, mineralization, and/or osteoclastogenesis using agents identified as described herein.

Abstract: This invention demonstrates that KRC molecules have multiple important functions as modulating agents in regulating a wide variety of cellular processes including bone formation and mineralization. TGF-? signaling in osteoblasts promotes the formation of a multimeric complex between KRC, Runx2, Smad3, and the E3 ubiquitin ligase, WWP1 which inhibits Runx2 function due to the ability of WWP1 to promote Runx2 polyubiquitination and proteasome-dependent degradation. Furthermore, KRC and WWP1 form a complex with RSK2 which promotes RSK2 phosphorylation and inhibits RSK2 function due to the ability of WWP 1 to promote RSK2 ubiquitination. Methods for identifying modulators of KRC activity are provided. Methods for modulating an immune response, bone formation and mineralization, and KRC-associated disorders using agents that modulate KRC expression and/or activity are also provided.

Abstract: The present invention is based, at least in part, on the identification of molecules involved in the differentiation and/or activity of osteoblasts and osteoclasts. Accordingly, the present invention provides methods of identifying modulators of bone formation, mineralization, and/or osteoclastogenesis and methods for treating disorders that would benefit from modulation of bone formation, mineralization, and/or osteoclastogenesis using agents identified as described herein. The target biomolecules of these methods are, for example, the osteoblast regulators TA0K2 or DLG1 or P1N1 or LYK5 or M0BKL2C or MAP4K2 or PACSIN2 or DCAMKLI or D0CK4 or PARO1 or TA0K3 or TRPV6 or CLK1 or AAK1 or PRKCA or AKAP8 or DGKJ or SMARCB1 or CIB2 or STIK33 or STK 39 or NRGN or PIK3R1 or RASSF5 or FRAPI or STK3S or LATSI or LATS2 or STK38L or GEFT or TNNI3K or STK4 or RAF1 or ARFI or CI7orf1 or SMURF2. The assays may involve mesenchymal cells.

Abstract: This invention demonstrates that KRC molecules have multiple important functions as modulating agents in regulating a wide variety of cellular processes including bone formation and mineralization. TGF-? signaling in osteoblasts promotes the formation of a multimeric complex between KRC, Runx2, Smad3, and the E3 ubiquitin ligase, WWP1 which inhibits Runx2 function due to the ability of WWP1 to promote Runx2 polyubiquitination and proteasome-dependent degradation. Furthermore, KRC and WWP1 form a complex with RSK2 which promotes RSK2 phosphorylation and inhibits RSK2 function due to the ability of WWP 1 to promote RSK2 ubiquitination. Methods for identifying modulators of KRC activity are provided. Methods for modulating an immune response, bone formation and mineralization, and KRC-associated disorders using agents that modulate KRC expression and/or activity are also provided.

Abstract: The present invention is based, at least in part, on the identification of molecules involved in the differentiation and/or activity of osteoblasts and osteoclasts. Accordingly, the present invention provides methods of identifying modulators of bone formation, mineralization, and/or osteoclastogenesis and methods for treating disorders that would benefit from modulation of bone formation, mineralization, and/or osteoclastogenesis using agents identified as described herein.