PTH1-34 promotes osteoblast formation through Beclin1-dependent autophagic activation.

INTRODUCTION: PTH1-34 can stimulate osteoblast formation, which contributes to the improvement of bone loss. PTH1-34 can activate autophagy, and autophagy plays a key role in osteoblast formation. This study aimed to explore the role of autophagy in PTH1-34-regulated osteoblastogenesis. MATERIALS AND METHODS: In this study, the mice treated with ovariectomy (OVX mice) were used to observe the effect of PTH1-34 on the formation and autophagy of osteoblasts in trabecular bone in vivo. Osteoblast precursor cell line MC3T3-E1 was treated with PTH1-34, and then the autophagic parameters of osteoblast precursors (including autophagic proteins and autophagosome formation) were detected using Western Blotting and Transmission Electron Microscopy. Next, after using autophagic pharmacological inhibitor (3-MA) and silencing vectors of autophagic molecule Beclin1 to downregulate autophagic activity, the parameters related to osteogenesis (including ALP staining intensity, ALP activity, cell proliferation and osteoblastic protein expression) were evaluated using corresponding assays. RESULTS: In vivo results showed that PTH1-34 not only improved bone loss caused by OVX but also restored Beclin1 expression and autophagic activity of immature osteoblasts in bone tissues. In vitro assays also showed that treatment of PTH1-34 enhanced the autophagy in osteoblast precursors. Moreover, under PTH1-34 intervention, the upregulated osteogenic parameters were reversed by autophagic inhibition with 3-MA. Of note, Beclin1 silencing can recover the osteogenic activity enhanced by PTH1-34. CONCLUSION: PTH1-34 can enhance the autophagic activity of osteoblast precursors, which is involved in PTH1-34-regulated osteoblast formation. Furthermore, Beclin1, as a key autophagic regulator, plays a pivotal role in PTH1-34-regulated osteoblast precursor autophagy and osteoblastogenesis.

JNK1 regulates RANKL-induced osteoclastogenesis via activation of a novel Bcl-2-Beclin1-autophagy pathway.

JNK1 plays an important role in osteoclastogenesis in response to the osteoclastogenic cytokine receptor activator for nuclear factor-κB ligand (RANKL). JNK1 is widely accepted as an autophagy regulator under stress conditions. However, the role of JNK1-mediated autophagy in osteoclastogenesis remains largely unknown. In the current study, our data showed that JNK1 inhibition by a pharmacological inhibitor or RNA interference significantly reduced the autophagic response induced by RANKL in osteoclast precursors (OCPs) derived from bone marrow-derived macrophages. Overexpression of the key autophagy protein Beclin1 rescued autophagy deficiency and osteoclastogenesis in the presence of a JNK inhibitor (SP600125). In contrast, JNK activator (anisomycin)-induced autophagy was blocked by Beclin1 knockdown in OCPs. In addition, JNK1 inhibition increased apoptosis and blocked autophagy, whereas overexpression of Beclin1 reversed the enhanced apoptosis induced by JNK1 inhibition in OCPs. Furthermore, RANKL could induce the phosphorylation of Bcl-2, subsequently dissociating Beclin1 from the Bcl-2-Beclin1 complex, which could be blocked by JNK1 inhibition. Collectively, this study revealed that JNK1 regulated osteoclastogenesis by activating Bcl-2-Beclin1-autophagy signaling in addition to the classic c-Jun/activator protein 1 pathway, which provided the first evidence for the contribution of JNK1 signaling to OCP autophagy and the autophagic mechanism underlying JNK1-regulated osteoclastogenesis. An important osteoclastogenesis-regulating signaling pathway (JNK1-Bcl-2-Beclin1-autophagy activation) was identified, which provides novel potential targets for the clinical therapy of metabolic bone diseases.-Ke, D., Ji, L., Wang, Y., Fu, X., Chen, J., Wang, F., Zhao, D., Xue, Y., Lan, X., Hou, J. JNK1 regulates RANKL-induced osteoclastogenesis via activation of a novel Bcl-2-Beclin1-autophagy pathway.

Nbr1-regulated autophagy in Lactoferrin-induced osteoblastic differentiation.

The molecular mechanism of autophagy in Lactoferrin (LF) induced osteoblast differentiation is not fully demonstrated. In this study, alkaline phosphatase (ALP) activity, alizarin red S staining and ELISA were used to study N-terminal propeptide of type I procollagen (PINP) expression. mRFP-GFP-LC3 adenoviruses, mono-dansylcadaverine (MDC) staining, scanning electron microscopy, and western blot analysis was employed to probe the LF induced autophagy. The interaction between autophagy receptor Neighbor of Brca1 gene (Nbr1) and pp38 was studied. 3-methyladenine (3-MA) and chloroquine (CQ) could inhibit the activity of ALP, PINP and the autophagy in LF group. LF treatment could up-regulate and down-regulate the expressions of pp38 and Nbr1with a dose-dependent manner, respectively. LF could inhibit the recognition of pp38 and Nbr1. In addition, LF can prompt Nbr1-medicated autophagy and prevent pp38 degradation by autophagy. LF can induce Nbr1-mediated autophagy and inhibit pp38 entering into autophagy flux in the physiological process of osteoblast differentiation.Abbreviations: CQ:chloroquine；LF: Lactoferrin; 3-MA: 3-methyladenine; ALP: Alkaline phosphatase; ANOVA: Analysis of variance; CCK-8: Cell Counting Kit-8; LC3: Microtubule-associated protein light chain3; MDC: Monodansylcadaverine; Nbr1: neighbor of Brca1 gene; PINP: N-terminal propeptide of type I procollagen; PVDF: Polychlorotrifluoroethylene; pp38: phosphorylation p38; RAPA: Rapamycin; SDS: sodium dodecyl sulfate.

Characteristics of highly resilient therapists.

This qualitative study aimed to explore characteristics that sustain therapists' resilience over years of practice. Ten highly resilient therapists were recruited during two phases of sample screening: peer nomination and the use of quantitative scales. Data were collected through in-person interviews and analyzed using grounded theory. Results as characteristics showed that highly resilient therapists are (a) drawn to strong interpersonal relationships, (b) actively engage with self, (c) possess a core values and beliefs framework, and (d) desire to learn and grow. The authors identified a central characteristic that interlinks with each characteristic: have a strong web of vibrant connectedness. Implications for counselor resilience development, training, and supervision are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Exendin-4 enhances proliferation of senescent osteoblasts through activation of the IGF-1/IGF-1R signaling pathway.

A growing body of evidence indicates that treatment with glucagon-like peptide-1 (GLP-1) receptor agonists can be beneficial for patients with osteoporosis. However, the underlying mechanism by which GLP-1 receptor agonists improve osteoporosis remains unclear. In this study, we assessed the anti-osteoporosis effects of Exendin-4, a highly potent GLP-1 receptor agonist, using a rat senescent osteoblast model. We found that Exendin-4 improved proliferation of senescent osteoblasts, as indicated by MTT assay and ALP activity detection. RT-qPCR revealed that Exendin-4 up-regulated the expression of bone metabolism genes (OPG, RANKL, BGP) and down-regulated the expression of aging-related genes (p16, p21, p53). Meanwhile, we observed a sustained increase in IGF-1 receptor (IGF-1R) expression, and not GLP-1 receptor (GLP-1R) expression, in senescent osteoblasts treated with Exendin-4. Furthermore, intervention with Exendin-4 in senescent osteoblasts increased IGF-1, p-PI3K, and p-Akt protein levels, as shown by western blot analysis. Finally, downregulation of IGF-1 by RNAi inhibited the anti-osteoporosis effects of Exendin-4, which is associated with the IGF-1/PI3K/Akt signaling pathway. In summary, these results indicate that the GLP-1 receptor agonist Exendin-4 promotes proliferation of senescent osteoblasts by up-regulating IGF-1R expression and activating the IGF-1/PI3K/Akt signaling pathway, thereby preventing senile osteoporosis.

IL-17A regulates the autophagic activity of osteoclast precursors through RANKL-JNK1 signaling during osteoclastogenesis in vitro.

Interleukin-17A(IL-17A), a proinflammatory cytokine, may have effects on osteoclastic resorption in inflammation-mediated bone loss, including postmenopausal osteoporosis. IL-17A could alter autophagic activity among other tissues and cells, thereby causing corresponding lesions. The aim of this study was to clarify how IL-17A influenced osteoclastogenesis by regulating autophagy. The present study showed that IL-17A could facilitate osteoclast precursors (OCPs) autophagy and osteoclastogenesis at a low concentration. Furthermore, suppression of autophagy with chloroquine (CQ) or 3-MA could significantly attenuate the enhanced osteoclastogenesis by a low level of IL-17A. It was also found that a low level of IL-17A couldn't up-regulate OCPs autophagy after removal of RANKL(Receptor Activator for Nuclear Factor-κB Ligand), and JNK(c-Jun N-terminal kinase) inhibitor only inhibited autophagy at a low level of IL-17A. These results suggest that a low concentration of IL-17A is likely to promote autophagic activity via activating RANKL-JNK pathway during osteoclastogenesis.

Roscovitine Protects From Arterial Injury by Regulating the Expressions of c-Jun and p27 and Inhibiting Vascular Smooth Muscle Cell Proliferation.

PURPOSE: Roscovitine (Rosc) is a selective inhibitor of cyclin-dependent kinases (CDKs) and a promising therapy for various cancers. However, limited information is available on the biological significance of Rosc in vascular smooth muscle cells (VSMCs), the cell type critical for the development of proliferative vascular diseases. In this study, we address the effects of Rosc in regulating VSMC proliferation, both in vitro and in vivo, exploring the underlying molecular mechanisms. METHODS: The proliferations and cell-cycle distributions of in vitro cultured VSMCs, as well as several other cancer cell lines, were examined by cell-counting assay and flow cytometry, respectively. Molecular changes in various CDKs, cyclins, and other regulatory molecules were examined by reverse transcription polymerase chain reaction, Western blot, or immunocytochemistry. The in vivo effects of Rosc were examined on a carotid arterial balloon-injury model. RESULTS: Rosc significantly inhibited VSMC proliferation in response to serum or angiotensin II and arrested these cells at the G0/G1 phase. These changes were associated with a specific and robust decrease in CDK4, cyclin E, c-Jun, and a dramatic increase in p27kip1 in VSMCs, which was also translated in vivo and correlated with the protection of Rosc on injury-induced neointimal hyperplasia. CONCLUSIONS: Acting on distinct molecular targets in VSMCs versus cancer cells, Rosc inhibits VSMC proliferation and protects from proliferative vascular diseases.

Immunohistochemical identification of osteoclasts and multinucleated macrophages.

Osteoclasts are bone-resorbing multinuclear cells derived from hematopoietic stem cells which are specialised to carry out lacunar bone resorption. The immunophenotype of giant cell-containing bone lesions in a wide range of osteoclast-like giant cells was similarly assessed. Both multinucleated macrophages and osteoclasts were found to express CD68. Multinucleated macrophages, but not osteoclasts, expressed GrB and Ki67. CD13+/CD14+/CD68+/GrB-/Ki67-/CD56- all giant-cell lesions noted in giant cells of bone. Giant cells have an osteoclast phenotype in most giant cell-rich lesions of bone, which do not express the macrophage-associated antigens GrB and Ki67. Our results indicate that they are formed from osteoclast precursors of mononuclear phagocyte.

Lactoferrin promote primary rat osteoblast proliferation and differentiation via up-regulation of insulin-like growth factor-1 expression.

The aim of this study was to explore the effect of lactoferrin (LF) in primary fetal rat osteoblasts proliferation and differentiation and investigate the underlying molecular mechanisms. Primary rat osteoblasts were obtained from the calvarias of neonatal rats. Osteoblasts were treated with LF (0.1-1000 µg/mL), or OSI-906 [a selective inhibitor of insulin-like growth factor 1 (IGF-1) receptor and insulin receptor]. The IGF-1 was then knocked down by small hairpin RNA (shRNA) technology and then was treated with recombinant human IGF-1 or LF. Cell proliferation and differentiation were measured by MTT assay and alkaline phosphatase (ALP) assay, respectively. The expression of IGF-1 and IGF binding protein 2 (IGFBP2) mRNA were analyzed using real-time PCR. LF promotes the proliferation and differentiation of osteoblasts in a certain range (1-100 µg/mL) in time- and dose-dependent manner. The mRNA level of IGF-1 was significantly increased, while the expression of IGFBP2 was suppressed by LF treatment. Knockdown of IGF-1 by shRNA in primary rat osteoblast dramatically decreased the abilities of proliferation and differentiation of osteoblasts and blocked the proliferation and differentiation effect of LF in osteoblasts. OSI906 (5 µM) blocked the mitogenic and differentiation of LF in osteoblasts. Proliferation and differentiation of primary rat osteoblasts in response to LF are mediated in part by stimulating of IGF-1 gene expression and alterations in the gene expression of IGFBP2.

Lactoferrin inhibits apoptosis through insulin-like growth factor I in primary rat osteoblasts.

AIM: Excessive apoptosis of osteoblasts is the major cause of low bone mass, and bovine lactoferrin (bLF), an iron-binding glycoprotein, might protect osteoblastic cells from apoptosis induced by serum withdrawal. The aim of this study was to elucidate the mechanisms underlying the anti-apoptotic action of bLF in rat osteoblasts in vitro. METHODS: Primary rat osteoblasts were incubated in the presence of varying concentrations of bLF for 24 h. The expression of insulin-like growth factor I (IGF-I) and IGF-I receptor (IGF-IR) was measured uisng RT-PCR and Western blotting. Cell apoptosis was examined with flow cytometry. siRNAs targeting IGF-I was used in this study. RESULTS: Treatment of bLF (0.1-1000 µg/mL) dose-dependently increased the expression of IGF-I and IGF-IR in the osteoblasts. Treatment with bLF (10, 100 µg/mL) markedly inhibited the osteoblast apoptosis (with the rate of total apoptosis of 70% at 10 µg/mL), but the high concentration of bLF (1000 µg/mL) significantly promoted the osteoblast apoptosis. Knockdown of the IGF-I gene in osteoblasts with siRNA markedly increased the osteoblast apoptosis. CONCLUSION: Lactoferrin (10 and 100 µg/mL) effectively inhibits apoptosis of primary rat osteoblasts by upregulating IGF-I expression.

The Impact of Labor Force Participation on Elderly Health in China.

In the context of the deepening of population aging and the trial implementation of a progressive retirement delay policy in China, understanding the relationship between the labor force participation and health status of the elderly will not only enrich relevant research but also help the elderly better achieve their goals of active aging and aging. Using the 2018 China Health and Retirement Longitudinal Study, this paper first established multiple linear regression models to analyze the impact of labor force participation on the health status of elderly people in China and then established simultaneous equation models using households living on minimum living allowances and the community average of labor participation as instrumental variables to deal with the endogeneity caused by two-way causality. The findings confirmed significant positive correlations between labor force participation and physical and mental health, while caring for grandchildren and participating in social activities were found to be negatively moderated the relationship between labor force participation and the physical and mental health of older adults. The impact of labor force participation on the physical health status of older men and the mental health status of older women may be greater. In addition, labor force participation may have a greater impact on the physical health of the rural elderly, and its impact on mental health was not found to be statistically significant between urban and rural areas.

GPER1 contributes to T3-induced osteogenesis by mediating glycolysis in osteoblast precursors.

Triiodothyronine (T3) is critical to osteogenesis, which is the key factor in bone growth. Our transcriptomic and metabolomic analysis results indicated that T3 leads to enhanced expression of G protein-coupled estrogen receptor 1 (GPER1) as well as increases in glycolysis metabolite levels. Accordingly, our study aimed to explore the role of GPER1-mediated glycolysis in T3-regulated osteogenesis. The MC3T3-E1 cell line was used as an osteoblast precursor model. After treatment with T3, a GPER1-specific antagonist (G15) and inhibitor of glycolysis (3PO) were used to explore the roles of GPER1 and glycolysis in T3-regulated osteogenesis, as measured by ALP activity, Alizarin red staining intensity and osteogenic molecule expression. Our results showed that T3 promoted osteogenesis-related activity, which was reversed by treatment with G15. In addition, T3 enhanced the glycolytic potential and production of lactic acid (LD) in MC3T3-E1 cells, and treatment with G15 restored the aforementioned effects of T3. Ultimately, the pharmacological inhibition of glycolysis with 3PO blocked the ability of T3 to enhance osteogenic activities. In conclusion, GPER1 mediates glycolysis in osteoblast precursors, which is critical for T3-promoted osteogenesis.

Bovine lactoferrin improves bone mass and microstructure in ovariectomized rats via OPG/RANKL/RANK pathway.

AIM: Lactoferrin (LF), an 80-kDa iron-binding glycoprotein, is a pleiotropic factor found in colostrum, milk, saliva and epithelial cells of the exocrine glands. The aim of this study was to evaluate the effects of LF on the bones in ovariectomized (Ovx) rats and to identify the pathways that mediate the anabolic action of LF on the bones. METHODS: Female Sprague-Dawley rats (6-month-old) underwent ovariectomy, and were treated with different doses of LF (10, 100, 1000, and 2000 mg·kg(-1)·d(-1), po) or with 7ß-estradiol (0.1 mg·kg(-1), im, each week) as the positive control. By the end of 6 month-treatments, the bone mass and microstructure in the rats were scanned by micro-computed tomography (micro-CT), and the bone metabolism was evaluated with specific markers, and the mRNA levels of osteoprotegerin (OPG) and the receptor-activator of nuclear factor κB ligand (RANKL) in femur were measured using qRT-PCR. RESULTS: LF treatment dose-dependently elevated the bone volume (BV/TV), trabecular thickness (TbTh) and trabecular number (TbN), and reduced the trabecular separation (TbSp) in Ovx rats. Furthermore, higher doses of LF (1000 and 2000 mg·kg(-1)·d(-1)) significantly increased the bone mineral density (BMD) compared with the untreated Ovx rats. The higher doses of LF also significantly increased the serum levels of OC and BALP, and decreased the serum levels of ß-CTx and NTX. LF treatment significantly increased the OPG mRNA levels, and suppressed the RANKL mRNA levels, and the RANKL/OPG mRNA ratio in Ovx rats. CONCLUSION: Oral administration of LF preserves the bone mass and improves the bone microarchitecture. LF enhances bone formation, reduces bone resorption, and decreases bone mass loss, possibly through the regulation of OPG/RANKL/RANK pathway.

The Impact of Family Socioeconomic Status on Elderly Health in China: Based on the Frailty Index.

China is about to enter a moderate aging society. In the process of social and economic development, the family socioeconomic status and health status of the elderly have also changed significantly. Learning the impact of family socioeconomic status on elderly health can help them improve family socioeconomic status and better achieve healthy and active aging. Using the data of the Chinese Longitudinal Healthy Longevity Survey in 2018, this study firstly analyzed the impact of family socioeconomic status on elderly health using the multivariate linear regression model and quantile regression model, the heterogeneity of different elderly groups using subsample regression, and the mediation effects of three conditions associated with the family socioeconomic status of the elderly. The results show that family socioeconomic status has a negative effect on the frailty index, that is, it has a positive impact on elderly health. Family socioeconomic status has a higher positive impact on the health status of the middle and lower age elderly and rural elderly. Overall living status and leisure and recreation status both have mediation effects, while health-care status has no mediation effect.

Multidimensional energy poverty and depression among China's older adults.

Older adults often face more pronounced energy inequality in their daily lives, which is one of the reasons for their accumulation of stress or anxiety and may further aggravate their depression. Analyzing the relationship between energy poverty and the depression level of China's older adults will provide policy enlightenment for solving the problems of older adults' relative poverty, energy poverty, and mental poverty and thus promote happy and healthy aging. In this paper, using the data of China Health and Retirement Longitudinal Study in 2018, we used the entropy weighting method to objectively assign weights to 10 indicators reflecting the status of energy poverty and construct a multidimensional energy poverty index for older adults. First, we analyzed the relationship between multidimensional energy poverty and the depression levels of older adults using multiple linear regression model and quantile regression models. Next, we used instrumental variable linear regression model and instrumental variable quantile regression models for endogeneity tests. Then, we performed a robustness check by replacing the core explanatory variable. After that, we conducted heterogeneity analyses by residential area, type of residence, and solitary status. Finally, we analyzed the mediating role of life satisfaction using structural equation modeling. Multidimensional energy poverty has aggravated depression among older adults, and the effect is greater for older adults with higher depression levels. The effect of multidimensional energy poverty on depression is greater for older adults in western China, urban areas, and those who live alone. Multidimensional energy poverty has aggravated depression among older adults by reducing their life satisfaction.

Lactoferrin ameliorates aging-suppressed osteogenesis via IGF1 signaling.

Lactoferrin (LF) is an iron-binding glycoprotein that plays an important role in promoting bone formation and inhibiting bone resorption; however, its effects on senile osteoporosis remain unknown. This study aimed to investigate the effects and mechanism of LF intervention using a senile osteoporosis model (SAMP6 mice) and senescent osteoblasts. Micro-CT and hematoxylin and eosin staining demonstrated that the intragastric administration (2 g/kg/day) of LF could improve the bone mass and microstructure of SAMP6 mice. Furthermore, LF treatment improved bone metabolism and increased insulin-like growth factor 1 (Igf1) mRNA expression and activated phosphorylation status of AKT. Using osteoblasts passaged for ten generations as an in vitro senescence model, various markers associated with osteoblast formation and differentiation, as well as related indices of oxidative stress were analyzed. Our results revealed that after multiple generations, osteoblasts entered senescence, in conjunction with increased oxidative stress damage, reduced bone metabolism and enhanced expression of aging-related markers. While inhibiting oxidative stress, LF improved osteoblast proliferation by promoting the expression of osteogenesis markers, including alkaline phosphatase (ALP) activity, Igf1, bone gla protein (Bglap) and osteoprotegerin/receptor activator of nuclear factor-kB ligand (Opg/Rankl) mRNA and delayed senescence by decreasing the level of p16 and p21 expression. RNAI-mediated downregulation of IGF1 attenuated the effect of LF on osteogenesis. Therefore, the findings of the present study indicate that LF may promote osteogenesis via IGF1 signaling, thereby preventing senile osteoporosis.

Roscovitine attenuates intimal hyperplasia via inhibiting NF-κB and STAT3 activation induced by TNF-α in vascular smooth muscle cells.

Roscovitine is a selective CDK inhibitor originally designed as anti-cancer agent, which has also been shown to inhibit proliferation in vascular smooth muscle cells (VSMCs). However, its effect on vascular remodeling and its mechanism of action remain unknown. In our study, we created a new intimal hyperplasia model in male Sprague-Dawley rats by trypsin digestion method, which cause to vascular injury as well as the model of rat carotid balloon angioplasty. Roscovitine administration led to a significant reduction in neointimal formation and VSMCs proliferation after injury in rats. Western blot analysis revealed that, in response to vascular injury, TNF-α stimulation induced p65 and STAT3 phosphorylation and promoted translocation of these molecules into the nucleus. p65 can physically associate with STAT3 and bind to TNF-α-regulated target promoters, such as MCP-1 and ICAM-1, to initiate gene transcription. Roscovitine can interrupt activation of NF-κB and reduce expression of TNF-α-induced proinflammatory gene, thus inhibiting intimal hyperplasia. These findings provide a novel mechanism to explain the roscovitine-mediated inhibition of intimal hyperplasia induced by proinflammatory pathways.

Lactoferrin Induces Osteoblast Growth through IGF-1R.

Objectives. To investigate the role of the IGF-1R by which lactoferrin induces osteoblast growth. Methods. Osteoblast received 5 d lactoferrin intervention at a concentration of 0.1, 1, 10, 100, and 1000 µg/mL, and the IGF-1 and IGF-1R were detected using RT-PCR and western blot. The osteoblast into the control, 100 µg/mL lactoferrin, Neo-scramble (NS, empty vector), NS + 100 µg/mL lactoferrin, shIGF-1R and shIGF-1R + 100 µg/mL lactoferrin group. We test the apoptosis and proliferation and the level of PI3K and RAS in osteoblasts after 5 d intervention. Results. (1) 1, 10, 100, and 1000 µg/mL lactoferrin induced the expression of IGF-1 mRNA and protein. 10 µg/mL and 100 µg/mL lactoferrin induced the expression of IGF-1R mRNA and protein. (2) Lactoferrin (100 µg/mL) induced osteoblast proliferation while inhibiting apoptosis. Osteoblasts with silenced IGF-1R exhibited decreased proliferation but increased apoptosis. MMT staining and flow cytometry both indicated that there was no significant difference between the shIGF-1R group and the shIGF-1R + 100 µg/mL lactoferrin group. (3) Lactoferrin (100 µg/mL) induced PI3K and RAS phosphorylation and silence of IGF-1R resulted in decreased p-PI3K and p-RAS expression. Lactoferrin-treated shIGF-1R cells showed significantly higher level of p-PI3K and p-RAS when compared with shIGF-1R. Conclusion. Lactoferrin induced IGF-1/IGF-1R in a concentration-dependent manner. Lactoferrin promoted osteoblast proliferation while inhibiting apoptosis through IGF-1R. Lactoferrin activated PI3K and RAS phosphorylation via an IGF-1R independent pathway.

The effects of ApoE gene polymorphisms on lumbar spine bone mineral density and carotid atherosclerosis.

OBJECTIVES: We analyzed the correlation between osteoporosis and carotid atherosclerosis (CA) by exploring the effects of ApoE gene polymorphisms on bone mineral density (BMD) of the lumbar spine and CA. DESIGN AND METHODS: We selected 221 elderly Han male patients and divided them into four groups: control, CA, BMD↓, and CA+BMD↓ according to their carotid ultrasonography and lumbar BMD results. ApoE gene polymorphisms were examined in each group. RESULTS: The CA group had a higher incidence of ApoE4 isoforms compared to normal controls (P<0.05). The ApoE4 isoform incidence in the BMD↓ and BMD↓/CA groups showed no significant difference from control. ApoE4 genotype incidences in the CA group, BMD ↓ group, and CA/BMD ↓ group were not significantly different. CONCLUSION: The ApoE4 genotype may be a risk factor for carotid atherosclerosis, but is not correlated with bone mineral density (BMD) in the lumbar spine in elderly Han males.