Menatetrenone rescues bone loss by improving osteoblast dysfunction in rats immobilized by sciatic neurectomy

Iwasaki-Ishizuka, Yoshiko; Yamato, Hideyuki; Murayama, Hisashi; Ezawa, Ikuko; Kurokawa, Kiyoshi; Fukagawa, Masafumi

doi:10.1016/j.lfs.2004.12.001

Cited by 12 publications

(8 citation statements)

References 46 publications

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“…In the present study, we investigated the effects of vitamins K1, K2, and K3 on the differentiation and function of human primary osteoblasts (NHBC), since the evidence so far favors osteoblast lineage cells as targets of vitamin K, rather than a direct effect on osteoclasts (29,32,34,51,53,55). We showed previously that NHBC acquire osteocyte-like properties and an antiosteoclastogenic phenotype in response to the anabolic compound strontium ranelate (5).…”

Section: Discussionmentioning

confidence: 99%

“…Osteocytes appear to initiate bone repair in response to microcracks (12), as well as new bone formation in response to increased loading of bone (37,49). Vitamin K2 has also been proven effective in preventing bone loss in rat immobilization/disuse models (28,29). In both of these examples of pathological bone loss, there is evidence for a central role for osteocyte apoptosis, and it is therefore plausible that the action of vitamin K was at least partly at the level of the osteocyte.…”

Section: Discussionmentioning

confidence: 99%

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Vitamin K promotes mineralization, osteoblast-to-osteocyte transition, and an anticatabolic phenotype by γ-carboxylation-dependent and -independent mechanisms

Atkins

Welldon

Wijenayaka

et al. 2009

American Journal of Physiology-Cell Physiology

116

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The vitamin K family members phylloquinone (vitamin K1) and the menaquinones (vitamin K2) are under study for their roles in bone metabolism and as potential therapeutic agents for skeletal diseases. We have investigated the effects of two naturally occurring homologs, phytonadione (vitamin K1) and menatetrenone (vitamin K2), and those of the synthetic vitamin K, menadione (vitamin K3), on human primary osteoblasts. All homologs promoted in vitro mineralization by these cells. Vitamin K1-induced mineralization was highly sensitive to warfarin, whereas that induced by vitamins K2 and K3 was less sensitive, implying that gamma-carboxylation and other mechanisms, possibly genomic actions through activation of the steroid xenobiotic receptor, are involved in the effect. The positive effect on mineralization was associated with decreased matrix synthesis, evidenced by a decrease from control in expression of type I collagen mRNA, implying a maturational effect. Incubation in the presence of vitamin K2 or K3 in a three-dimensional type I collagen gel culture system resulted in increased numbers of cells with elongated cytoplasmic processes resembling osteocytes. This effect was not warfarin sensitive. Addition of calcein to vitamin K-treated cells revealed vitamin K-dependent deposition of mineral associated with cell processes. These effects are consistent with vitamin K promoting the osteoblast-to-osteocyte transition in humans. To test whether vitamin K may also act on mature osteocytes, we tested the effects of vitamin K on MLO-Y4 cells. Vitamin K reduced receptor activator of NF-kappaB ligand expression relative to osteoprotegerin by MLO-Y4 cells, an effect also seen in human cultures. Together, our findings suggest that vitamin K promotes the osteoblast-to-osteocyte transition, at the same time decreasing the osteoclastogenic potential of these cells. These may be mechanisms by which vitamin K optimizes bone formation and integrity in vivo and may help explain the net positive effect of vitamin K on bone formation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Vitamin K promotes mineralization, osteoblast-to-osteocyte transition, and an anticatabolic phenotype by γ-carboxylation-dependent and -independent mechanisms

Atkins

Welldon

Wijenayaka

et al. 2009

American Journal of Physiology-Cell Physiology

116

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“…However, the 8-wk duration of ovariectomy and unilateral cast immobilization applied in that study was too short to cover the entire critical period of axial growth of rat. Sciatic neurectomy enables longer intervention periods than cast immobilization and is widely used in experimental bone research (3,10,11,50,52). Therefore, we hypothesized here that, by selectively removing the influences of estrogen (E) and locomotive loading (L) factors over the entire period of postnatal axial growth, it is possible to determine their respective effects and possible interaction on the development of the diaphyseal geometry of rat femur.…”

mentioning

confidence: 99%

The effects of loading and estrogen on rat bone growth

Leppänen¹,

Sievänen

Jokihaara

et al. 2010

Journal of Applied Physiology

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This study evaluated the contributions of locomotive loading and estrogen to the development of diaphysis of rat femur. A randomized 2x2 study design was used. Altogether, 70 female Sprague-Dawley rats were used, of which 10 were euthanized at entry. Of the remaining rats, 16 served as controls, and the rest, 44, underwent a unilateral sciatic neurectomy. The effect of estrogen was removed by ovariectomizing one-half of the neurectomized rats. After 27 wk, the animals were euthanized, and the femora were excised. Irrespective of loading or estrogen, the femur length and mineral mass increased by 142 and 687%, respectively. Axial growth was not modulated either by locomotive loading or estrogen, but the loading resulted in direction-specific changes in the cross-sectional geometry. The estrogen-related gains were evident on the endocortical surface, while the loading-related gains occurred on the periosteal surface. The loading and estrogen were significantly associated with increased bone strength (21 and 15%, respectively) in the mediolateral direction, but not in the anteroposterior direction. Axial growth and accrual of bone mineral mass of the rat femur are largely independent of locomotive loading or estrogen, whereas these factors specifically account for the femur function, as either a mechanical lever or a mineral reservoir for reproduction, respectively.

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“…Furthermore, Iwasaki-Ishizaka et al50 demonstrated that vitamin K 2 increased the BMD of the distal femoral metaphysis by increasing bone formation and decreasing bone resorption in rats with sciatic neurectomy induced-bone loss. In addition, vitamin K 2 increased γ-carboxylated osteocalcin levels and decreased undercarboxylated osteocalcin levels in the serum.…”

Section: Effects Of Vitamin K2 On the Development Of Osteopenia In Ratsmentioning

confidence: 99%

Effects of Vitamin K2 on the Development of Osteopenia in Rats as the Models of Osteoporosis

2006

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Vitamin K2 is widely used for the treatment of osteoporosis in Japan. To understand the effects of vitamin K2 on bone mass and bone metabolism, we reviewed its effects on the development of osteopenia in rats, which characterizes models of osteoporosis. Vitamin K2 was found to attenuate the increase in bone resorption and/or maintain bone formation, reduce bone loss, protect against the loss of trabecular bone mass and its connectivity, and prevent the decrease in strength of the long bone in ovariectomized rats. However, combined treatment of bisphosphonates and vitamin K2 had an additive effect in preventing the deterioration of the trabecular bone architecture in ovariectomized rats, while the combined treatment of raloxifene and vitamin K2 improved the bone strength of the femoral neck. The use of vitamin K2 alone suppressed the increase in trabecular bone turnover and endocortical bone resorption, which attenuated the development of cancellous and cortical osteopenia in orchidectomized rats. In addition, vitamin K2 inhibited the decrease in bone formation in prednisolone-treated rats, thereby preventing cancellous and cortical osteopenia. In sciatic neurectomized rats, vitamin K2 suppressed endocortical bone resorption and stimulated bone formation, delaying the reduction of the trabecular thickness and retarding the development of cortical osteopenia. Vitamin K2 also prevented the acceleration of bone resorption and the reduction in bone formation in tail-suspended rats, which counteracted cancellous bone loss. Concomitant use of vitamin K2 with a bisphosphonate ameliorated the suppression of bone formation and more effectively prevented cancellous bone loss in tail-suspended rats. Vitamin K2 stimulated renal calcium reabsorption, retarded the increase in serum parathyroid hormone levels, and attenuated cortical bone loss primarily by suppressing bone resorption in calcium-deficient rats while maintaining the strength of the long bone in rats with magnesium deficiency. These findings suggest that vitamin K2 may not only stimulate bone formation, but may also suppress bone resorption. Thus, vitamin K2 could regulate bone metabolism in rats, which represented the various models of osteoporosis. However, the effects of vitamin K2 on bone mass and bone metabolism seem to be modest.

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Menatetrenone rescues bone loss by improving osteoblast dysfunction in rats immobilized by sciatic neurectomy

Cited by 12 publications

References 46 publications

Vitamin K promotes mineralization, osteoblast-to-osteocyte transition, and an anticatabolic phenotype by γ-carboxylation-dependent and -independent mechanisms

Vitamin K promotes mineralization, osteoblast-to-osteocyte transition, and an anticatabolic phenotype by γ-carboxylation-dependent and -independent mechanisms

The effects of loading and estrogen on rat bone growth

Effects of Vitamin K2 on the Development of Osteopenia in Rats as the Models of Osteoporosis

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