Insulin-like growth factor-1 cytokines cross-talk in type 1 diabetes mellitus: Relationship to microvascular complications and bone mineral density

AboElAsrar, Mohammed A; Elbarbary, Nancy Samir; El‐Shennawy, Dina; Omar, Amin M.

doi:10.1016/j.cyto.2012.03.019

Cited by 49 publications

(50 citation statements)

References 64 publications

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“…Previous studies reported lower serum IGF-1 along with higher inflammatory cytokines and lower bone mineral density in T1DM patients with poor glycemic control than those with good glycemic control [29–31]. We first confirmed that the proliferation and osteogenesis of these diabetic BMSCs and PDCs were differentially impaired and these impairments were exacerbated in high glucose cultures.…”

Section: Introductionsupporting

confidence: 76%

“…As IGF-1, an anabolic factor for skeletal growth [36], is reduced in T1DM patients with poor glycemic control [29–31], we examined whether supplementing osteogenic cultures of diabetic BMSCs and PDCs with potent osteogenic factor rhBMP-2/7 heterodimer [28] and/or rhIGF-1 may rescue their osteogenesis. In normal glucose (5.5 mM) osteogenic culture, rhBMP2/7 supplement enhanced the osteogenesis of diabetic BMSCs and PDCs in a dose-dependent manner, as indicated by alizarin red staining (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Impaired osteogenesis of T1DM bone marrow-derived stromal cells and periosteum-derived cells and their differential in-vitro responses to growth factor rescue

et al. 2017

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BackgroundPoor bone quality, increased fracture risks, and impaired bone healing are orthopedic comorbidities of type 1 diabetes (T1DM). Standard osteogenic growth factor treatments are inadequate in fully rescuing retarded healing of traumatic T1DM long bone injuries where both periosteal and bone marrow niches are disrupted. We test the hypotheses that osteogenesis of bone marrow-derived stromal cells (BMSCs) and periosteum-derived cells (PDCs), two critical skeletal progenitors in long bone healing, are both impaired in T1DM and that they respond differentially to osteogenic bone morphogenetic proteins (BMPs) and/or insulin-like growth factor-1 (IGF-1) rescue.MethodsBMSCs and PDCs were isolated from Biobreeding Diabetes Prone/Worcester rats acquiring T1DM and normal Wistar rats. Proliferation, osteogenesis, and adipogenesis of the diabetic progenitors were compared with normal controls. Responses of diabetic progenitors to osteogenesis rescue by rhBMP-2/7 heterodimer (45 or 300 ng/ml) and/or rhIGF-1 (15 or 100 ng/ml) in normal and high glucose cultures were examined by alizarin red staining and qPCR.ResultsDiabetic BMSCs and PDCs proliferated slower and underwent poorer osteogenesis than nondiabetic controls, and these impairments were exacerbated in high glucose cultures. Osteogenesis of diabetic PDCs was rescued by rhBMP-2/7 or rhBMP-2/7 + rhIGF-1 in both normal and high glucose cultures in a dose-dependent manner. Diabetic BMSCs, however, only responded to 300 ng/nl rhBMP-2/7 with/without 100 ng/ml rhIGF-1 in normal but not high glucose osteogenic culture. IGF-1 alone was insufficient in rescuing the osteogenesis of either diabetic progenitor. Supplementing rhBMP-2/7 in high glucose osteogenic culture significantly enhanced gene expressions of type 1 collagen (Col 1), osteocalcin (OCN), and glucose transporter 1 (GLUT1) while suppressing that of adipogenic marker peroxisome proliferator-activated receptor gamma (PPARγ) in diabetic PDCs. The same treatment in high glucose culture only resulted in a moderate increase in Col 1, but no significant changes in OCN or GLUT1 expressions in diabetic BMSCs.ConclusionsThis study demonstrates more effective osteogenesis rescue of diabetic PDCs than BMSCs by rhBMP-2/7 with/without rhIGF-1 in a hyperglycemia environment, underscoring the necessity to tailor biochemical therapeutics to specific skeletal progenitor niches. Our data also suggest potential benefits of combining growth factor treatment with blood glucose management to optimize orthopedic therapeutic outcomes for T1DM patients.

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Section: Introductionsupporting

confidence: 76%

Section: Resultsmentioning

confidence: 99%

Impaired osteogenesis of T1DM bone marrow-derived stromal cells and periosteum-derived cells and their differential in-vitro responses to growth factor rescue

et al. 2017

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“…Autoimmune destruction of the pancreatic beta cells by infiltrating immune cells triggers pancreatic and systemic upregulation of inflammatory cytokines in humans [43-45] and in animal models of STZ-induced diabetes [46]; moreover, T1D subjects with poor glycemic control exhibit higher levels of inflammation compared to well-controlled subjects [45]. Inflammatory cytokines that are systemically upregulated in T1D subjects, such as tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1) and interleukin 6 (IL-6) have been demonstrated to have negative effects on osteoblast proliferation and differentiation in vitro , as well as inhibition of bone healing in vivo [47-50].…”

Section: Effects Of Type 1 Diabetes On Osteoblastsmentioning

confidence: 99%

Effects of Type 1 Diabetes on Osteoblasts, Osteocytes, and Osteoclasts

Kalaitzoglou

Popescu

Bunn

et al. 2016

Curr Osteoporos Rep

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Purpose of review To describe the effects of Type 1 diabetes on bone cells. Recent findings Type 1 diabetes (T1D) is associated with low bone mineral density, increased risk of fractures and poor fracture healing. Its effects on the skeleton were primarily attributed to impaired bone formation, but recent data suggests that bone remodeling and resorption are also compromised. The hyperglycemic and inflammatory environment associated with T1D impacts osteoblasts, osteocytes and osteoclasts. The mechanisms involved are complex; insulinopenia, pro-inflammatory cytokine production and alterations in gene expression are a few of the contributing factors leading to poor osteoblast activity and survival and, therefore, poor bone formation. In addition, the observed sclerostin level increase accompanied by decreased osteocyte number and enhanced osteoclast activity in T1D results in uncoupling of bone remodeling. Summary T1D negatively impacts osteoblasts and osteocytes whereas its effects on osteoclasts are not well characterized, although the limited studies available indicate increased osteoclast activity, favoring bone resorption.

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“…In diabetic mice, the upregulation of specific transcription factors is attenuated, resulting in deficiency in conversion of mesenchymal cells to osteoblasts [13,14,16]. Moreover, diabetes interferes with hormonal responsiveness not only to sex hormones but also to calciotrophic hormones such as calcitonin or IGF1 [17]. We found that high glucose (HG) affects the response of human-derived cultured bone cells to estrogens by downregulating it, which is relevant at least to some of the important factors existing in diabetes.…”

Section: Introductionmentioning

confidence: 91%

Estrogens and Hyperglycemic Modulation of mRNAs Expressions Involved in Bone Metabolism: An Overshadowed Association?

Sömjen

Katzburg²,

Sharon³

et al. 2013

Connective Tissue Research

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Human bone cell line (SaOS2) express different mRNAs involved in bone biology and physiology such as estrogen receptor α (ERα), estrogen receptor β (ERβ), vitamin D receptor (VDR), 1α, 25 hydroxy vitamin D(3) hydroxylase (1OHase) as well as 12 and 15 lipoxygenases (12LO and 15LO). These mRNAs are modulated by estrogenic compounds. Since the skeletal protective effects of estrogens are not discernible in diabetic women, we tested whether the expression of the parameters measured here and their modulations by estrogens, in SaOS2 cells grown in growth medium containing high glucose (HG; 9.0 g/L; 44 mM) compared to normal glucose (NG; 4.5 g/L; 22 mM). High Glucose (HG) significantly increased DNA synthesis and creatine kinase (CK) specific activity in SaOS2 cells. Stimulations of DNA but not of CK by E(2), by 4, 4', 4''-[4-propyl-(1H)-pyrazol-1, 3, 5- triyl] tris-phenol (PPT, ERα specific agonist), or by 2, 3-bis (4-hydroxyphenyl)-propionitrile (DPN, ERβ specific agonist), were abolished by HG. HG itself upregulated the expression of mRNA of 12LO and 15LO and upregulated to much less extent of ERβ and VDR, but had no effect on the expression of mRNA of ERα and 1OHase. The different hormonal treatments modulated the expressions of 12LO and 15LO mRNAs which was reduced in HG, whereas the induction of their products 12HETE and 15HETE was only slightly affected by HG. The exact mechanism of HG effects on bone cell responses is yet to be investigated and its relationship to human bone physiology is not yet clear.

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Insulin-like growth factor-1 cytokines cross-talk in type 1 diabetes mellitus: Relationship to microvascular complications and bone mineral density

Cited by 49 publications

References 64 publications

Impaired osteogenesis of T1DM bone marrow-derived stromal cells and periosteum-derived cells and their differential in-vitro responses to growth factor rescue

Impaired osteogenesis of T1DM bone marrow-derived stromal cells and periosteum-derived cells and their differential in-vitro responses to growth factor rescue

Effects of Type 1 Diabetes on Osteoblasts, Osteocytes, and Osteoclasts

Estrogens and Hyperglycemic Modulation of mRNAs Expressions Involved in Bone Metabolism: An Overshadowed Association?

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