title: Increased bone mass in mice after single injection of anti-receptor activator of nuclear factor-kappaB ligand-neutralizing antibody: evidence for bone anabolic effect of parathyroid hormone in mice with few osteoclasts.
abstract: Receptor activator of nuclear factor-κB ligand (RANKL) is a pivotal osteoclast differentiation factor. To investigate the effect of RANKL inhibition in normal mice, we prepared an anti-mouse RANKL-neutralizing monoclonal antibody (Mab, clone OYC1) and established a new mouse model with high bone mass induced by administration of OYC1. A single subcutaneous injection of 5 mg/kg OYC1 in normal mice significantly augmented the bone mineral density in the distal femoral metaphysis from day 2 to day 28. The OYC1 treatment markedly reduced the serum level of tartrate-resistant acid phosphatase-5b (TRAP-5b, a marker for osteoclasts) on day 1, and this level was undetectable from day 3 to day 28. The serum level of alkaline phosphatase (a marker for osteoblasts) declined significantly following the reduction of TRAP-5b. Histological analysis revealed few osteoclasts in femurs of the treated mice on day 4, and both osteoclasts and osteoblasts were markedly diminished on day 14. Daily injection of parathyroid hormone for 2 weeks increased the bone mineral density in trabecular and cortical bone by stimulating bone formation in the OYC1-treated mice. These results suggest that parathyroid hormone exerted its bone anabolic activity in mice with few osteoclasts. The mouse anti-RANKL neutralizing antibody OYC1 may be a useful tool to investigate unknown functions of RANKL in vivo.
authors.affiliation: Nagahama Institute for Biochemical Science, Nagahama Branch, Oriental Yeast Co., Limited, 50 Kano-cho Nagahama, Shiga 526-0804, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Furuya
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mori
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ninomiya
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tomimori
authors.forename: Sakae
authors.initials: S
authors.lastname: Tanaka
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Udagawa
authors.forename: Kohji
authors.initials: K
authors.lastname: Uchida
authors.forename: Hisataka
authors.initials: H
authors.lastname: Yasuda
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D000943:Antigens, Differentiation / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects*; D005260:Female; D005269:Femur / Q000378:metabolism* / Q000473:pathology; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D013997:Time Factors
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D057134:Antibodies, Neutralizing; D000943:Antigens, Differentiation; D007527:Isoenzymes; D010281:Parathyroid Hormone; D053245:RANK Ligand; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase