Local administration of calcitriol positively influences bone remodeling and maturation during restoration of mandibular bone defects in rats

Liu, Hongrui; Cui, Jian; Feng, Wei; Lv, Shengyu; Du, Juan; Sun, Jing; Han, Xiuchun; Wang, Zhenming; Li, Xiong; Yimin,; Oda, Kimimitsu; Amizuka, Norio; Li, Minqi

doi:10.1016/j.msec.2014.12.064

Cited by 26 publications

(15 citation statements)

References 52 publications

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“…Although our studies showed that the 1,25(OH) 2 D-mediated inhibition of inflammation impaired fracture healing, a diametrically opposed result from a locally high-dose 1,25(OH) 2 D treatment was found in experimental colitis (an animal model of human inflammatory bowel disease) and experimental allergic encephalomyelitis (an animal model of human multiple sclerosis) (45,46). The different outcomes of the 1,25(OH) 2 D treatment in these 2 distinct inflammatory conditions signify the importance of local tissue microenvironment for tissue repair (46,47).…”

Section: Role Of 125(oh) 2 D Treatment Under Vitamin D-sufficient Comentioning

confidence: 56%

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1,25-Dihydroxyvitamin D suppresses M1 macrophages and promotes M2 differentiation at bone injury sites

et al. 2018

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An indispensable role of macrophages in bone repair has been well recognized. Previous data have demonstrated the copresence of M1 macrophages and mesenchymal stem cells (MSCs) during the proinflammatory stage of bone repair. However, the exact role of M1 macrophages in MSC function and bone repair is unknown. This study aimed to define the role of M1 macrophages at bone injury sites via the function of 1,25-Dihydroxyvitamin D (1,25[OH]2D) in suppressing M1 but promoting M2 differentiation. We showed that 1,25(OH)2D suppressed M1 macrophage-mediated enhancement of MSC migration. Additionally, 1,25(OH)2D inhibited M1 macrophage secretion of osteogenic proteins (i.e., Oncostatin M, TNF-α, and IL-6). Importantly, the 1,25(OH)2D-mediated suppression of osteogenic function in M1 macrophages at the proinflammatory stage was associated with 1,25(OH)2D-mediated reduction of MSC abundance, compromised osteogenic potential of MSCs, and impairment of fracture repair. Furthermore, outside the proinflammatory stage, 1,25(OH)2D treatment did not suppress fracture repair. Accordingly, our data support 2 conclusions: (a) M1 macrophages are important for the recruitment and osteogenic priming of MSCs and, hence, are necessary for fracture repair, and (b) under vitamin D-sufficient conditions, 1,25(OH)2D treatment is unnecessary and can be detrimental if provided during the proinflammatory stage of fracture healing.

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Section: Role Of 125(oh) 2 D Treatment Under Vitamin D-sufficient Comentioning

confidence: 56%

“…The PCR conditions were 10 minutes at 95°C followed by 40 cycles of 10 seconds at 95°C and 15 seconds at 60°C. The relative expression level of a gene was determined using ΔΔCt method and normalized to GAPDH (45).…”

Section: Methodsmentioning

confidence: 99%

1,25-Dihydroxyvitamin D suppresses M1 macrophages and promotes M2 differentiation at bone injury sites

et al. 2018

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“…Calcitriol, the bioactive form of vitamin D, was used throughout this study to optimize the screening procedure, but also to validate the mineralizing operculum as a suitable system to monitor osteogenic bioactivities. Calcitriol is a well-known osteogenic and anti-osteoporotic compound (Bernabei, 2014) that stimulates osteoblastic growth and differentiation, and therefore bone formation in vivo (Liu et al, 2015) and mineralization in vitro (Woeckel et al, 2010). Calcitriol also increases bone formation in zebrafish skeletal structures, such as in the perichordal sheath and coracoid processes, after exposure from 3 to 9 dpf (at concentrations higher than entopterygoids and ceratohyal after exposure from 5 to 10 dpf (at 200 ng/mL) (Aceto et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

The zebrafish operculum: A powerful system to assess osteogenic bioactivities of molecules with pharmacological and toxicological relevance

Tarasco

Laizé

Cardeira

et al. 2017

Comparative Biochemistry and Physiology Part C: Toxicology &

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Bone disorders affect millions of people worldwide and available therapeutics have a limited efficacy, often presenting undesirable side effects. As such, there is a need for novel molecules with bone anabolic properties. The aim of this work was to establish a rapid, reliable and reproducible method to screen for molecules with osteogenic activities, using the zebrafish operculum to assess bone formation. Exposure parameters were optimized through morphological analysis of the developing operculum of larvae exposed to calcitriol, a molecule with known pro-osteogenic properties. An exposure of 3 days initiated at 3 days post-fertilization was sufficient to stimulate operculum formation, while not affecting survival or development of the larvae. Dose-dependent pro-and anti-osteogenic effects of calcitriol and cobalt chloride, respectively, demonstrated the sensitivity of the method and the suitability of the operculum system. A double transgenic reporter line expressing fluorescent markers for early and mature osteoblasts was used to gain insights into the effects of calcitriol and cobalt at the cellular level, with osteoblast maturation shown to be stimulated and inhibited, respectively, in the operculum of exposed fish. The zebrafish operculum represents a consistent, robust and rapid screening system for the discovery of novel molecules with osteogenic, anti-osteoporotic or osteotoxic activity.

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“…SD standard deviation; af 9100; cells 9400 upregulated the expression of interferon-beta (IFN-beta), which are key regulators of osteoclast formation (Takasu et al 2006;Sakai et al 2009). In addition, our previous studies reported that local administration of calcitriol promoted osteogenesis and mineralization, which could be promising for the restoration of mandibular bone defects Liu et al 2015). More interestingly, in thyroparathyroidectomized rats infused with parathyroid hormone (PTH), systemically administered calcitriol inhibited PTH-induced bone resorption at a physiological dose and stimulated bone resorption at a toxic dose .…”

Section: Discussionmentioning

confidence: 99%

Histochemical examination of the effects of high-dose 1,25(OH)2D3 on bone remodeling in young growing rats

Sun

Wang

et al. 2016

J Mol Hist

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Vitamin D has an anabolic effect on bone developmental processes and is involved in maintaining skeletal integrity. In recent years, pediatric cases of vitamin D intoxication have attracted attention. Therefore, the aim of this study was to investigate the influence of long-term administration of physiologically-high-dose calcitriol (1,25(OH)2D3) on bone remodeling in young developing rats. Neonatal rats received once-daily subcutaneous injection of calcitriol (250 ng/kg body weight), or PBS only as a control, for 3 weeks. At 1, 2 and 4 weeks' post-administration, rats were sacrificed and fixed by transcardial perfusion with 4 % paraformaldehyde, following which tibiae were extracted for histochemical analysis. Compared with the control group, the number of tartrate-resistant acid phosphatase- and Cathepsin K-positive osteoclasts were significantly increased, and the expression of alkaline phosphatase in osteoblasts was decreased in trabecular bone of rats administered high-dose 1,25(OH)2D3, leading to decreased trabecular bone volume. In addition, the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) was increased, while that of osteoprotegerin was weaker in osteoblasts in the experimental group compared with the control group. Moreover, there was weaker immunoreactivity for EphrinB2 in osteoclasts and EphB4 in osteoblasts of trabecular bone in the experimental group compared with the control group. These findings suggest that long-term use of physiologically-high dose calcitriol may result in bone loss through RANKL/RANK/osteoprotegerin and EphrinB2-EphB4 signaling pathways, and that these negative effects could continue after drug withdrawal. Therefore, optimal limits for vitamin D administration need to be established for children and adolescents.

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Local administration of calcitriol positively influences bone remodeling and maturation during restoration of mandibular bone defects in rats

Cited by 26 publications

References 52 publications

1,25-Dihydroxyvitamin D suppresses M1 macrophages and promotes M2 differentiation at bone injury sites

1,25-Dihydroxyvitamin D suppresses M1 macrophages and promotes M2 differentiation at bone injury sites

The zebrafish operculum: A powerful system to assess osteogenic bioactivities of molecules with pharmacological and toxicological relevance

Histochemical examination of the effects of high-dose 1,25(OH)2D3 on bone remodeling in young growing rats

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