title: Vitamin D endocrine system and osteoclasts.
abstract: Vitamin D was discovered as an anti-rachitic agent preventing a failure in bone mineralization, but it is now established that the active form of vitamin D3 (1α,25(OH)2D3) induces bone resorption. Discovery of the receptor activator of nuclear factor -κB ligand (RANKL) uncovered the molecular mechanism by which 1α,25(OH)2D3 stimulates bone resorption. Treating osteoblastic cells with 1α,25(OH)2D3 stimulates RANKL expression, which in turn induces osteoclastogenesis. Nevertheless, active vitamin D compounds such as calcitriol (1α,25(OH)2D3), alfacalcidol (1α(OH)D3) and eldecalcitol (1α,25-dihydroxy-2β-(3-hydroxypropoxy) vitamin D3) have been used as therapeutic drugs for osteoporosis, as they increase bone mineral density (BMD) in osteoporotic patients. Paradoxically, the increase in BMD is caused by the suppression of bone resorption. Several studies have been performed to elucidate the mechanism by which active vitamin D compounds suppress bone resorption in vivo. Our study showed that daily administration of eldecalcitol to mice suppressed neither the number of osteoclast precursors in the bone marrow nor the number of osteoclasts formed in ex vivo cultures. Eldecalcitol administration suppressed RANKL expression in osteoblasts. This review discusses how the difference between in vitro and in vivo effects of active vitamin D compounds on bone resorption is induced.
authors.affiliation: Institute for Oral Science, Matsumoto Dental University , Nagano, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Department of Biochemistry, Matsumoto Dental University , Nagano, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Udagawa
authors.affiliation: Department of Biochemistry, Matsumoto Dental University , Nagano, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Udagawa
authors.affiliation: Research Center for Genomic Medicine, Saitama Medical University , Saitama, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Suda