Controlling osteogenesis by inhibition of osteogenic suppressors

1. A method for identifying agents that promote osteogenesis, the methods comprising,

(a) contacting a plurality of agents to a potassium channel, subfamily T, member 1 (“KCNT1”) polypeptide comprising SEQ ID NO:178;

(b) measuring the activity of the polypeptide;

(c) selecting at least one of the plurality of agents, wherein the selected agent(s) inhibit the activity of the polypeptide; and

(d) measuring the ability of the selected agent(s) to promote osteogenesis, thereby identifying agents that promote osteogenesis.

2. The method of claim 1 , wherein the polypeptide is expressed in a host cell.

3. The method of claim 2 , wherein the measuring step (b) comprises measuring the expression of the polypeptide.

4. The method of claim 3 , wherein measuring the expression comprises measuring the level of transcription.

5. The method of claim 2 , wherein the cells are mammalian cells.

6. The method of claim 1 , wherein the measuring step (d) is carried out in vitro.

7. The method of claim 1 , wherein the measuring step (d) is carried out in vivo.

8. The method of claim 1 , further comprising contacting the plurality of agents to a solute carrier family 12 (sodium/potassium/chloride transporters), member 2 (SLC12A2) polypeptide comprising SEQ ID NO:180.

9. The method of claim 1 , further comprising contacting the plurality of agents to a polypeptide selected from the group consisting of: SEQ ID NO:152 (GNAS complex locus (GNAS)), SEQ ID NO:156 (adenosine kinase (ADK)), SEQ ID NO:158 (purinergic receptor P2Y, G-protein coupled, 11 (P2RY11)), SEQ ID NO:180 (solute carrier family 12 (sodium/potassium/chloride transporters), member 2 (SLC12A2)) and SEQ ID NO:238 (putative glialbiastoma cell differentiation-related (GBDR1)).

10. The method of claim 1 , further comprising contacting the plurality of agents to a polypeptide selected from the group consisting of: SEQ ID NO:180 (solute carrier family 12 (sodium/potassium/chloride transporters), member 2 (SLC12A2)), SEQ ID NO:152 (GNAS complex locus (GNAS)), SEQ ID NO:154 (adenylate cyclase 8 (ADCY8)), SEQ ID NO:156 (adenosine kinase (ADK)), SEQ ID NO:158 (purinergic receptor P2Y, G-protein coupled, 11 (P2RY11)), SEQ ID NO:160 (olfactory receptor, family 12, subfamily D, member 3 (OR12D3)), SEQ ID NO:162 (olfactory receptor OR52I2, SEQ ID NO:164 (olfactory receptor OR51G2), SEQ ID NO:166 (olfactory receptor OR2M4), SEQ ID NO:168 (olfactory receptor OR4F29, SEQ ID NO:170 (integrin, alpha L (ITGAL)), SEQ ID NO:172 (integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor) (ITGA2)), SEQ ID NO:174 (angiopoietin-like factor (CDT6)), SEQ ID NO:176 (angiopoietin-like 2 (ANGPTL2)), SEQ ID NO:182 (mitochondrial carrier family protein (MCFP)), SEQ ID NO:184 (B-cell CLL/lymphoma 2 (BCL2)), SEQ ID NO:186 (BCL2-like 2 (BCL2L2)), SEQ ID NO:188 (nuclear receptor subfamily 2, group E, member 3 (NR2E3)), SEQ ID NO:190 (putative leukocyte platelet-activating factor receptor (HUMNPIIY20)), SEQ ID NO:192 (chemokine (C- C motif) ligand 5 (CCL5)), SEQ ID NO:194 (dual specificity phosphatase 6 (DUSP6)1, SEQ ID NO:196 (serine/threonine kinase 10 (STK10)), SEQ ID NO:198 (putative dipeptidase (LOC64174)), SEQ ID NO:200 (phospholipase A2, group IID (PLA2G2D)), SEQ ID NO:202 (Cytochrome P450 (CYP4Z1)), SEQ ID NO:204 (aldo-keto reductase family 1, member C2 (AKR1C2)), SEQ ID NO:206 (methylmalonyl Coenzyme A mutase (MUT)), SEQ ID NO:208 (dopamine beta-hydroxylase (dopamine beta-monooxygenase) (DBH)), SEQ ID NO:210 (transketolase-like 1 (TKTL1)), SEQ ID NO:212 (fumarylacetoacetate hydrolase (furmarylacetoacetase) (FAH)), SEQ ID NO:214 (polymerase (DNA directed), eta (POLH)), SEQ ID NO:216 (cyclin-dependent kinase inhibitor 2B (CDKN2B)), SEQ ID NO:218 (CDC14 cell division cycle 14 homolog B (CDC14B)), SEQ ID NO:220 (Machado-Joseph disease (ataxin 3) (MJD)), SEQ ID NO:222 (baculoviral IAP repeat-containing 4 (BIRC4)), SEQ ID NO:224 (deafness, autosomal dominant 5 (DFNA5)), SEQ ID NO:226 (PHD finger protein 1 (PHF1)), SEQ ID NO:228 (T-box 3 (ulnar mammary syndrome) (TBX3)), SEQ ID NO:230 (praja 2, RING-H2 motif containing (PJA2), SEQ ID NO:232 (down regulated in lung cancer (HLCDGP1)), SEQ ID NO:238 (putative glialblastoma cell differentiation-related (GBDR1)), SEQ ID NO:240 (similar to semaphorin cytoplasmic domain-associated protein 3B (LOC341549)), SEQ ID NO:242 (ankyrin repeat and SOCS box-containing 11 (ASB11)), SEQ ID NO:244 (similar to Interferon-induced protein with tetratricopeptide repeats 1 (IFIT-1)), SEQ ID NO:246 (cartilage oligomeric matrix protein (pseudoachondroplasia) (COMP)), SEQ ID NO:248 (hypothetical protein BC009732 (LOC133308)), SEQ ID NO:250 (hypothetical protein MGC42105, SEQ ID NO:252 (hypothetical protein MGC15875, SEQ ID NO:254 (hypothetical protein FLJ386281), SEQ ID NO:259 (hypothetical protein LOC 114971), and SEQ ID NO:261 (DKFZP727G051 protein).