Gender-Specific Differences in the Skeletal Response to Continuous PTH in Mice Lacking the IGF1 Receptor in Mature Osteoblasts

Babey, Muriel; Wang, Yongmei; Kubota, Takuo; Fong, Chak; Menendez, Alicia; Elalieh, Hashem; Bikle, Daniel D.

doi:10.1002/jbmr.2433

Cited by 15 publications

(13 citation statements)

References 39 publications

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“…We concluded that icariin can affect the proliferation of osteoblasts by promoting DNA synthesis. During early stages of osteoblast differentiation, osteoblasts synthesize ALP and other osteoblastic differentiation markers, ultimately leading to the induction of extracellular matrix calcification ( Babey et al, 2015 ). In this study, the ALP activity was inhibited by treated with 0.1 mg/mL vancomycin, and effectively elevated by icariin during osteoblast differentiation.…”

Section: Discussionmentioning

confidence: 99%

Icariin Enhances Bone Repair in Rabbits with Bone Infection during Post-infection Treatment and Prevents Inhibition of Osteoblasts by Vancomycin

Zhang¹,

Shen

Mao³

et al. 2017

Front. Pharmacol.

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Vancomycin is an effective antibiotic for treatment of bone infection caused by Staphylococcus aureus, however, a high local concentration of vancomycin might induce a delay in bone union. Icariin has been reported to suppress osteoclastogenes and promote osteogenesis. Our study aimed to investigate the effect of icariin on bone repair after anti-infection treatment in vivo and to explore the resisting effect of icariin on rat calvarial osteoblasts (ROBs) inhibited with high doses of vancomycin. Rabbits with bone infection of S. aureus were treated with implanted vancomycin-calcium sulfate (VCS) and icariin at 10.86 mg/kg/day for consecutive 8 weeks. Micro-CT, morphology, blood biochemistry were evaluated. In addition, ROBs were treated with vancomycin and icariin at different doses. Cell proliferation and differentiation capabilities, BMP2, Runx2, OPG, RANKL mRNA levels and protein expression were assessed. The results indicated that high dose of vancomycin significantly decreased bone mass and inhibited osteocalcin secretion; icariin increased these indicators compared with the single vancomycin treatment. Over 0.1 mg/mL of vancomycin inhibited the proliferation and differentiation of ROBs, while icariin resisted the inhibition of vancomycin by regulating cell cycle and promoting the Alkaline phosphatase (ALP) activity. Moreover, icariin promote bone formation by up-regulating BMP2/Runx2 and OPG/RANKL pathways. Icariin exhibited osteoplastic properties on osteoblasts that had been inhibited with high doses of vancomycin. Therefore, icariin is helpful for post-infection treatment of bone infection.

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Section: Discussionmentioning

confidence: 99%

Icariin Enhances Bone Repair in Rabbits with Bone Infection during Post-infection Treatment and Prevents Inhibition of Osteoblasts by Vancomycin

Zhang¹,

Shen

Mao³

et al. 2017

Front. Pharmacol.

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“…The use of genetically modified or disease specific model mouse, or PTH (1–84) might be more suitable to elucidate bone fracture healing in patients with hyperparathyroidism, rather than exogenous recombinant PTH 1–34 (teriparatide) infusion. Finally, since gender-specific differences in the skeletal response to continuous PTH have been identified, fracture healing in women should also be verified 58 .…”

Section: Discussionmentioning

confidence: 99%

Continuous infusion of PTH1–34 delayed fracture healing in mice

Yukata

Kanchiku

Egawa

et al. 2018

Sci Rep

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Hyperparathyroidism, which is increased parathyroid hormone (PTH) levels in the blood, could cause delayed or non-union of bone fractures. But, no study has yet demonstrated the effects of excess continuous PTH exposure, such as that seen in hyperparathyroidism, for fracture healing. Continuous human PTH1–34 (teriparatide) infusion using an osmotic pump was performed for stabilized tibial fractures in eight-week-old male mice to determine the relative bone healing process compared with saline treatment. Radiographs and micro-computed tomography showed delayed but increased calcified callus formation in the continuous PTH1–34 infusion group compared with the controls. Histology and quantitative histomorphometry confirmed that continuous PTH1–34 treatment significantly increased the bone callus area at a later time point after fracture, since delayed endochondral ossification occurred. Gene expression analyses showed that PTH1–34 resulted in sustained Col2a1 and reduced Col10a1 expression, consistent with delayed maturation of the cartilage tissue during fracture healing. In contrast, continuous PTH1–34 infusion stimulated the expression of both Bglap and Acp5 through the healing process, in accordance with bone callus formation and remodeling. Mechanical testing showed that continuously administered PTH1–34 increased the maximum load on Day 21 compared with control mice. We concluded that continuous PTH1–34 infusion resulted in a delayed fracture healing process due to delayed callus cell maturation but ultimately increased biomechanical properties.

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“…Gender disparity in fracture risk stems from differences in peak bone mass accrual, bone size, and geometry (50) . Sex steroids that essentially drive skeletal variations in men and women integrate systemic cues such as that from vitamin D, IGF/GH, and PTH to dictate dimorphism at the cellular level (19,(51)(52)(53) .…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, sex differences in the cellular function of osteoblasts and osteoclasts have been attributed to differences in the bone phenotype of male and female mice (17)(18)(19)(20) . Differences in bone quality also contribute to the gender disparities in fracture risk.…”

Section: Discussionmentioning

confidence: 99%

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TGFβ regulation of perilacunar/canalicular remodeling is sexually dimorphic

Dole

Yee

Mazur

et al. 2019

Preprint

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1.AbstractBone fragility is the product of defects in bone mass and bone quality, both of which show sex-specific differences. Despite this, the cellular and molecular mechanisms underpinning the sexually dimorphic control of bone quality remain unclear, limiting our ability to effectively prevent fractures, especially in postmenopausal osteoporosis. Recently, using male mice, we found that systemic or osteocyte-intrinsic inhibition of TGFβ signaling, achieved using the 9.6-kb DMP1 promoter-driven Cre recombinase (TβRIIocy−/− mice), suppresses osteocyte perilacunar/canalicular remodeling (PLR) and compromises bone quality. Since systemic TGFβ inhibition more robustly increases bone mass in female than male mice, we postulated that sex-specific differences in bone quality could likewise result, in part, from dimorphic regulation of PLR by TGFβ. Moreover, since lactation induces PLR, we examined the effect of TGFβ inhibition on the female skeleton during lactation. In contrast to males, female mice that possess an osteocyte-intrinsic defect in TGFβ signaling were protected from TGFβ-dependent defects in PLR and bone quality. The expression of requisite PLR enzymes, the lacuno-canalicular network, and the flexural strength of female TβRIIocy−/− bone was intact. With lactation, however, bone loss, and induction in PLR and osteocytic parathyroid hormone type I receptor (PTHR1) expression, were suppressed in TβRIIocy−/− bone, relative to wild-type. Indeed, differential control of PTHR1 expression, by TGFβ and other factors, may contribute to dimorphism in PLR regulation in male and female TβRIIocy−/− mice. These findings provide key insights into the sex-based differences in osteocyte PLR that underlie bone quality and highlight TGFβ signaling as a crucial regulator of lactation-induced PLR.

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Gender-Specific Differences in the Skeletal Response to Continuous PTH in Mice Lacking the IGF1 Receptor in Mature Osteoblasts

Cited by 15 publications

References 39 publications

Icariin Enhances Bone Repair in Rabbits with Bone Infection during Post-infection Treatment and Prevents Inhibition of Osteoblasts by Vancomycin

Icariin Enhances Bone Repair in Rabbits with Bone Infection during Post-infection Treatment and Prevents Inhibition of Osteoblasts by Vancomycin

Continuous infusion of PTH1–34 delayed fracture healing in mice

TGFβ regulation of perilacunar/canalicular remodeling is sexually dimorphic

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