OPG ABROGATES ALCOHOL-INDUCED BONE LOSS IN MICE
1263
1
7. Dai J, Lin D, Zhang J, Habib P, Smith P, Murtha J, Fu Z, Yao 33. Bolon B, Carter C, Daris M, Morony S, Capparelli C, Hsieh A,
Z, Qi Y, Keller ET 2000 Chronic alcohol ingestion induces
osteoclastogenesis and bone loss through IL-6 in mice. J Clin
Invest 106:887–895.
Mao M, Kostenuik P, Dunstan CR, Lacey DL, Sheng JZ 2001
Adenoviral delivery of osteoprotegerin ameliorates bone re-
sorption in a mouse ovariectomy model of osteoporosis. Mol
Ther 3:197–205.
1
8. Watzl B, Lopez M, Shahbazian M, Chen G, Colombo LL,
Huang D, Way D, Watson RR 1993 Diet and ethanol modulate 34. Bekker PJ, Holloway D, Nakanishi A, Arrighi M, Leese PT,
immune responses in young C57BL/6 mice. Alcohol Clin Exp
Dunstan CR 2001 The effect of a single dose of osteoprotegerin
Res 17:623–630.
in postmenopausal women. J Bone Miner Res 16:348–360.
9. Wang Y, Watson RR 1994 Chronic ethanol consumption prior 35. Capparelli C, Kostenuik PJ, Morony S, Starnes C, Weimann B,
1
2
to retrovirus infection alters cytokine production by thymo-
cytes during murine AIDS. Alcohol 11:361–365.
0. Jilka RL, Weinstein RS, Takahashi K, Parfitt AM, Manolagas
SC 1996 Linkage of decreased bone mass with impaired
Van G, Scully S, Qi M, Lacey DL, Dunstan CR 2000 Osteo-
protegerin prevents and reverses hypercalcemia in a murine
model of humoral hypercalcemia of malignancy. Cancer Res
60:783–787.
osteoblastogenesis in a murine model of accelerated senes- 36. Zhang J, Dai J, Qi Y, Lin DL, Smith P, Strayhorn C, Mizokami
cence. J Clin Invest 97:1732–1740.
1. Lee SK, Goldring SR, Lorenzo JA 1995 Expression of the
calcitonin receptor in bone marrow cell cultures and in bone:
A, Fu Z, Westman J, Keller ET 2001 Osteoprotegerin inhibits
prostate cancer-induced osteoclastogenesis and prevents pros-
tate tumor growth in the bone. J Clin Invest 107:1235–1244.
2
2
A specific marker of the differentiated osteoclast that is regu- 37. Honore P, Luger NM, Sabino MA, Schwei MJ, Rogers SD,
lated by calcitonin. Endocrinology 136:4572–4581.
2. Kimmel DB, Bozzato RP, Kronis KA, Coble T, Sindrey D,
Kwong P, Recker RR 1993 The effect of recombinant human
Mach DB, O’Keefe P, F., Ramnaraine ML, Clohisy DR,
Mantyh PW 2000 Osteoprotegerin blocks bone cancer-induced
skeletal destruction, skeletal pain and pain-related neurochem-
ical reorganization of the spinal cord. Nat Med 6:521–528.
8. Luger NM, Honore P, Sabino MA, Schwei MJ, Rogers SD, Mach
DB, Clohisy DR, Mantyh PW 2001 Osteoprotegerin diminishes
advanced bone cancer pain. Cancer Res 61:4038–4047.
(1–84) or synthetic human (1-34) parathyroid hormone on the
3
3
skeleton of adult osteopenic ovariectomized rats. Endocrinol-
ogy 132:1577–1584.
2
2
3. Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H,
Meunier PJ, Ott SM, Recker RR 1987 Bone histomorphom-
etry: Standardization of nomenclature, symbols, and units.
Report of the ASBMR Histomorphometry Nomenclature
Committee. J Bone Miner Res 2:595–610.
4. Haeckel R, Bucklitsch I 1987 The comparability of ethanol
concentrations in peripheral blood and saliva. The phenome-
non of variation in saliva to blood concentration ratios. J Clin
Chem Clin Biochem 25:199–204.
9. Morony S, Capparelli C, Sarosi I, Lacey DL, Dunstan CR,
Kostenuik PJ 2001 Osteoprotegerin inhibits osteolysis and
decreases skeletal tumor burden in syngeneic and nude mouse
models of experimental bone metastasis. Cancer Res 61:4432–
4
436.
4
4
4
0. Clohisy DR, Ramnaraine ML, Scully S, Qi M, Van G, Tan HL,
Lacey DL 2000 Osteoprotegerin inhibits tumor-induced oste-
oclastogenesis and bone tumor growth in osteopetrotic mice.
J Orthop Res 18:967–976.
1. Pepersack T, Fuss M, Otero J, Bergmann P, Valsamis J,
Corvilain J 1992 Longitudinal study of bone metabolism after
ethanol withdrawal in alcoholic patients. J Bone Miner Res
2
2
5. Winek CL, Esposito FM 1987 The validity of urine alcohol
analysis in drunk drivers. Leg Med 97–106.
6. Fuller K, Wong B, Fox S, Choi Y, Chambers TJ 1998 TRANCE
is necessary and sufficient for osteoblast-mediated activation of
bone resorption in osteoclasts. J Exp Med 188:997–1001.
7. Nakashima T, Kobayashi Y, Yamasaki S, Kawakami A, Egu-
chi K, Sasaki H, Sakai H 2000 Protein expression and func-
tional difference of membrane-bound and soluble receptor
activator of NF-kappaB ligand: Modulation of the expression
by osteotropic factors and cytokines. Biochem Biophys Res
Commun 275:768–775.
8. Jilka RL, Weinstein RS, Bellido T, Roberson P, Parfitt AM,
Manolagas SC 1999 Increased bone formation by prevention
of osteoblast apoptosis with parathyroid hormone. J Clin In-
vest 104:439–446.
9. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS,
Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shi-
mamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trai
LG, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes
TM, Hill D, Pattison W, Campbell P, Boyle WJ 1997 Osteo-
protegerin: A novel secreted protein involved in the regulation
of bone density. Cell 89:309–319.
0. Yasuda H, Shima N, Nakagawa N, Mochizuki SI, Yano K, Fujise
N, Sato Y, Goto M, Yamaguchi K, Kuriyama M, Kanno T,
Murakami A, Tsuda E, Morinaga T, Higashio K 1998 Identity of
osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin
7
:383–387.
2. Morony S, Capparelli C, Lee R, Shimamoto G, Boone T,
Lacey DL, Dunstan CR 1999 A chimeric form of osteoprote-
gerin inhibits hypercalcemia and bone resorption induced by
IL-1beta, TNF-alpha, PTH, PTHrP, and 1, 25(OH)2D3. J Bone
Miner Res 14:1478–1485.
3. Emery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Sil-
verman C, Dul E, Appelbaum ER, Eichman C, DiPrinzio R,
Dodds RA, James IE, Rosenberg M, Lee JC, Young PR 1998
Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL.
J Biol Chem 273:14363–14367.
4. Truneh A, Sharma S, Silverman C, Khandekar S, Reddy MP,
Deen KC, McLaughlin MM, Srinivasula SM, Livi GP, Mar-
shall LA, Alnemri ES, Williams WV, Doyle ML 2000
Temperature-sensitive differential affinity of TRAIL for its
receptors. DR5 is the highest affinity receptor. J Biol Chem
2
4
4
2
2
2
75:23319–23325.
4
5. Kido J, Yamauchi N, Ohishi K, Kataoka M, Nishikawa S,
Nakamura T, Kadono H, Ikedo D, Ueno A, Nonomura N,
Okuyama A, Nagata T 1997 Inhibition of osteoblastic cell
differentiation by conditioned medium derived from the hu-
man prostatic cancer cell line PC-3 in vitro. J Cell Biochem
3
6
7:248–256.
(OPG): A mechanism by which OPG/OCIF inhibits osteoclasto-
genesis in vitro. Endocrinology 139:1329–1337.
3
1. Bateman TA, Dunstan CR, Ferguson VL, Lacey DL, Ayers
RA, Simske SJ 2000 Osteoprotegerin mitigates tail
suspension-induced osteopenia. Bone 26:443–449.
2. Min H, Morony S, Sarosi I, Dunstan CR, Capparelli C, Scully
S, Van G, Kaufman S, Kostenuik PJ, Lacey DL, Boyle WJ,
Simonet WS 2000 Osteoprotegerin reverses osteoporosis by
inhibiting endosteal osteoclasts and prevents vascular calcifi-
Address reprint requests to:
Evan T. Keller, D.V.M., Ph.D.
Room 5304 CCGCB, Box 0940
500 East Medical Center Drive
3
1
Ann Arbor, MI 48109-0940, USA
cation by blocking a process resembling osteoclastogenesis. J Received in original form August 13, 2001; in revised form Jan-
Exp Med 192:463–474. uary 13, 2002; accepted February 6, 2002.