Osteoprotegerin binding proteins and receptors

摘要

A novel polypeptide, osteoprotegerin binding protein, involved in osteoclast maturation has been identified based upon its affinity for osteoprotegerin. Nucleic acid sequences 5 encoding the polypeptide, or a fragment, analog or derivative thereof, vectors and host cells for production, methods of preparing osteoprotegerin binding protein, and binding assays are also described. Compositions and methods for the treatment of bone diseases such as osteoporosis, bone loss due to arthritis or metastasis, hypercalcemia, and Paget's disease are also provided. Receptors for osteoprotegerin binding proteins are also 10 described. The receptors, and agonists and antagonist thereof, may be used to treat bone diseases. CD 0 n m--i Y r- N u UA u ~ E-1 H E-44 04 Uf) U U U U~~ 0 C-) U 4 0W9 a)Nr-4 U r-4 U ~ ul 0K~ I E- OU>1 Hk Ln 0 0 0 U~ Ur aQ)c ry EA 0 00 -i U fc uU H- 0 0 k 0 4-J HO0 ) u U 1l: oU a4E4 4 u 0 U - 0 U i4 E-4 U) U 0 )- - 0 UkAU E0 0 0)uufz U 0 U 0km Uc! U 0' CD U< UW1 - E-A~- 0k Kc 0 U Ut-P 0 0 U oo U P U Ok Uk UrH U U H- L U H- U U E- 0 ~ ~ O >1 U 'Tj 0~E- H )O-Ur-4 H- U 4 H 00 U 0 U (Dcn o uU)P f 0 0 >Uu-I < -- Uk U H- 0 P UU 0U U0 0Ll 0 0 H U " 9- UCN U w (D U U4 00 a 0U0 0 U UUr-i U 01 0 U rH ,I Hf 0 0 HHi E-i 00 0 U2 U>1 0 0 C9 0 U Or- U 0 U -H a4 0 LnG G C)) C4C)0(D r4 >fl m E r E-1 E- lca a > 0C inLr -4 Q E-4 Q Oc! 0 O4 -4 E4 a)C : E-41L F:0U E1 ltU u~ 00&Au)L E-1 'A4W >1 E -au o 4 Or-- CD- 0r OW OWQ)Ln fz4 0 E-1 U) c: 0 r--4 0000 u (5 X u ~ u a (a HG UO O ' <: 00 r-IA H Oj 0~ >1 E-1 Or CDr-i~ U0 O9 u 0 0 0 0 0 041 n OW(Dfl Or-- H ~ t Hr-I (9 ) U r 0:1) () 00~~~ C:H)4O-r-i 0 0:1 aW E-i O n HW Ow O r) H-ilr 0 >1 ow 004 H6i4 H 0 in 0 in) 00 c) 0)EAp4-) r-H UZ: 111E-A >1 E- 0 U()0 C) E4 Or-I E-4 >lcc0) u (1 <0 U a rin4 00 0 ~ &4 U)Hr-I 0-J O -t3 H>1 > x~W u 0 E- U) O <0 HO ,,4 -i &lH00G E- (0r CJO) C:) 0/i 00 0a< ) 0< Op 0t 9 c > OU- r- 00)rI0 -40 00 0 < H uCT r-4 E0 u-Q 0~ 0>u a) cl oip( U P4 () H 0 F4 p) U)r Hu OuE4 : 0 P mM 0 com &4 ~ -~ 0 UN :: LI 0 >1 >1 a)w -, > ~U) u >1-4C: H r-I u4 t~o E4 H < c qH a)1 O1 U) -I EA V) W 0 0 H ':E-' 0~~ E-4 0 00 e j U-) >1 r ) OCN 0> 0 E-t H m 0 O j n p ) P (d -- I E-i M A D n E- T 0 > > < X CLLa E-4cGE-4 H ::j Ln 0 U a) EA ~ ~ (D CDpH >1 0 >1 0 0 Pom E-4 U OrH &I Hm PW OW n 4EA -U CN HU) p U) u4 rl EAH 4 D Pr OW ~ ~ - mr ~4 e~ P4 C o ~ ~OU>i E-1 Q)c) l<>1 u 4 Hr u u -4a)r-H U 4 O 4 U c' U P4-E- r-4 r-4 I r--4 E--4 E-4 UH E- P E-4E-4 Or-I 0>1 H Or-i0 U U H-4 cU H E-4r-H a) 4 1 u u E- H00 q H- H- U H U U H: E-H 0 U Uu H-4a) Crn E-4U Hr-I O H i~~ i 0 - 0 U) I< 0 E-U 00D0 0 H- E-4H 04 Lnu O c U) H-- H- H-l u ;j u 04 U- 0 u Ok~~U ,l-U) Hr0- 'I 0 U4 0 Ha) Ha) E-4 H 0 E- 1 P~ 0 ~ Hn 0) H E-- xlU cr >10 H- 0E-(3 U i 040l U4 4 >) ri o Lf r- (3 L IC - r-4 0 E- u H D~ E- (9 p Hi FH H U P p E-1H~ 0 H - E- H HE1 H 4 H U 0 H (D 0 < U E- X4 Hl<~~ H & A 0 c UvX E-f~ H 0 C9 0 U 0 H 4 E-4 H&4 09E-1 G 0 H u (9 4 H -U 0 E ( H H4 (9 -H, 0 0H 0 E4 U U 0 4 E 0 0 0 U - E- (94 0 pz E-4~ H- H - 4 F, H 0 H- H< Q H U C-4 H -ft 0 0 U -H E-G u E-1~ EA E E4 E- U - U H HD 0 U- H t 0 H U E- H- U U0. u u (9i 0 9 E-1 E- E- (D 0 &q HI uC E- U 0x E-- 0E-4H H-i H U E- 0 -0 ~ 0 1 E, - 11 Ul H U 0 I- Un 0- - CN0 0 ~ C H H H 0- E-4 H H H H H H H E- HE-1~ U H H HE-1 UE- E-4H H H H E- H 4 E- 0 -0 H E-4 E4 Ep E- H -H U (5