Abnormalities of Insulin-Like Growth Factor-I Signaling and Impaired Cell Proliferation in Osteoblasts from Subjects with Osteoporosis

Perrini, Sebastio; Natalicchio, Annalisa; Laviola, Luigi; Cignarelli, Angelo; Melchiorre, M; Stefano, Francesca De; Caccioppoli, Cristina; Leonardini, Anna; Martemucci, S; Belsanti, G; Miccoli, Sara; Ciampolillo, Anna; Corrado, A; Cantatore, Francesco Paolo; Giorgino, Francesco

doi:10.1210/en.2007-1349

Cited by 45 publications

(37 citation statements)

References 48 publications

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“…In bone, the balance between bone matrix synthesising osteoblast and bone resorbing osteoclast activity can be influenced by local and systemic factors, in physiological as well as in pathological conditions, leading to bone remodelling imbalanced towards increased bone resorption (Neve et al, 2011). Osteoblasts play a crucial role in controlling bone remodelling (Beil et al, 2008;Corrado et al, 2005;Dequeker et al, 1993;El Miedany et al, 2000;Hilal et al, 1998;Lajeunesse and Reboul, 2003;Perrini et al, 2008;Walsh et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Osteoblasts with impaired spreading capacity benefit from the positive charges of plasma polymerised allylamine

Kunz

Rebl²,

Quade³

et al. 2015

eCM

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Bone diseases such as osteoporosis, osteoarthritis and rheumatoid arthritis, impinge on the performance of orthopaedic implants by impairing bone regeneration. For this reason, the development of effective surface modifications supporting the ingrowth of implants in morbid bone tissue is essential. Our study is designed to elucidate if cells with restricted cell-function limiting adhesion processes benefit from plasma polymer deposition on titanium. We used the actin filament disrupting agent cytochalasin D (CD) as an experimental model for cells with impaired actin cytoskeleton. Indeed, the cell's capacity to adhere and spread was drastically reduced due to shortened actin filaments and vinculin contacts that were smaller. The coating of titanium with a positively charged nanolayer of plasma polymerised allylamine (PPAAm) abrogated these disadvantages in cell adhesion and the CD-treated osteoblasts were able to spread significantly. Interestingly, PPAAm increased spreading by causing enhanced vinculin number and contact length, but without significantly reorganising actin filaments. PPAAm with the monomer allylamine was deposited in a microwave-excited low-pressure plasma-processing reactor. Cell physiology was monitored by flow cytometry and confocal laser scanning microscopy, and the length and number of actin filaments was quantified by mathematical image processing. We showed that biomaterial surface modification with PPAAm could be beneficial even for osteoblasts with impaired cytoskeleton components. These insights into in vitro conditions may be used for the evaluation of future strategies to design implants for morbid bone tissue.

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Section: Introductionmentioning

confidence: 99%

Osteoblasts with impaired spreading capacity benefit from the positive charges of plasma polymerised allylamine

Kunz

Rebl²,

Quade³

et al. 2015

eCM

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“…synergistically with IGF-1 to induce osteogenesis in vitro, and IGF-1 expression may be increased by LIPUS in vitro, we questioned whether LIPUS on intact bone would regulate IRS-1 and ERK-1/2 expression and activation, which are proteins that act on IGF-1 signaling and induce osteogenesis [17,28,30,43].…”

Section: Discussionmentioning

confidence: 99%

“…IRS-1 participates in IGF-1 signaling pathways, cellular proliferation, and extracellular matrix synthesis and is indispensable for maintaining bone turnover, growth, and repair in response to hormonal stimulation [29,30,34]. IRS-1 expression behaved similarly to FAK expression at 7 and 14 days, indicating LIPUS acts on IRS-1 synthesis, probably as a result of mechanically induced increased IGF-1 expression [28].…”

Section: Discussionmentioning

confidence: 99%

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Low-intensity Ultrasound Increases FAK, ERK-1/2, and IRS-1 Expression of Intact Rat Bones in a Noncumulative Manner

Gusmão

Pauli

Saad

et al. 2010

Clinical Orthopaedics &Amp; Related Research

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Background Low-intensity pulsed ultrasound stimulation (LIPUS) reportedly increases osteogenesis in fracture models but fails in intact bone, suggesting LIPUS does not act on mechanotransduction and growth factor pathways of intact bone. Questions/Purposes We asked whether daily 20-minute LIPUS applied to intact tibias would act on bone proteins involved in mechanotransduction (focal adhesion kinase [FAK], and extracellular signal-regulated kinase-1/2 [ERK-1/2]), and growth factor signaling (insulin receptor substrate-1 [IRS-1]) pathways at 7, 14, and 21 days of treatment.Methods Immunoblotting was performed to detect FAK, ERK-1/2, and IRS-1 expression and activation from the stimulated intact tibias at 7, 14, and 21 days of daily 20-minute LIPUS. Results LIPUS increased FAK expression (at 7 days), ERK-1/2 (at 14 days), and IRS-1 (at 7 days), but expression decreased 7 days later, indicating a noncumulative effect of LIPUS. As only FAK expression was detected at 21 days, these observations suggest LIPUS influences nuclear reactions that may be modulated by a major cellular mechanism preferentially inhibiting IRS-1 expression and not FAK expression. Increased ERK-1/2 expression at 14 days suggests the differing mechanisms for promoting ERK-1/2, FAK, and IRS-1 syntheses. IRS-1 expression behaved similarly to FAK expression; therefore, LIPUS may modulate growth factor pathways. LIPUS increased sustained FAK and ERK-1/2 activation, but not IRS-1, suggesting sustained ERK-1/2 activation is not the result of mechanically induced growth factor activation. Conclusions LIPUS acts on mechanotransduction and growth factor pathways in intact bone in a noncumulative manner. Clinical relevance These data suggest LIPUS applied to intact bone acts on proteins involved in osteogenesis.

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“…The ability to produce a sufficient number of functionally active osteoblasts is pivotal to preserving bone mass and represents an essential step in the continuous, complex and well orchestrated process of bone remodeling [2]. There is now a growing body of evidence to suggest that BMSCs are critically involved in the pathogenesis of osteoporosis [3][4][5][6][7][8][9], thus implying that the structural abnormalities associated with osteoporotic bone maybe as a consequence of inadequacies in bone cell differentiation. This concept is further supported by findings from studies investigating the role of BMSCs in experimental models of osteoporosis and ageing.…”

Section: Introductionmentioning

confidence: 99%

Osteoanabolic effect of alendronate and zoledronate on bone marrow stromal cells (BMSCs) isolated from aged female osteoporotic patients and its implications for their mode of action in the treatment of age-related bone loss

et al. 2013

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In the present study, we evaluated the potential for aminobisphosphonates to enhance the development of bone-forming osteoblasts from progenitor cells isolated from aged female osteoporotic patients. The aminobisphosphonates tested significantly enhanced osteoblast formation and thus lend further insights into their possible mode of action in the treatment of osteoporosis. INTRODUCTION: The primary aim of this study was to evaluate the influence of aminobisphosphonates on the osteogenesis of human bone marrow stromal cells (hBMSCs) and mineralization of differentiating bone-forming cells isolated from osteoporotic patients. METHODS: The influence of aminobisphosphonate treatment on hBMSC osteogenesis was assessed by the quantitative measurement of alkaline phosphatase (ALP) activity, in addition to quantitative reverse transcription polymerase chain reaction and Western blot analysis of known osteogenic markers. Mineralized matrix formation by hBMSC-derived osteoblasts was visualized and quantified using Alizarin red staining. RESULTS: hBMSC cultures treated with osteogenic medium supplemented with zoledronate demonstrated a significant increase in Alizarin red staining after 3 weeks as compared to cells cultured in osteogenic medium alone. Similarly, cultures of differentiating hBMSCs isolated from patients receiving alendronate treatment also demonstrated an increased propensity for mineralization, even in the absence of further in vitro stimulation by zoledronate. The stimulatory effects of aminobisphosphonate treatment on hBMSC-derived osteoblast-mediated mineralization were independent of any alterations in ALP activity, although significant decreases in the expression levels of osteopontin (SPP1) were evident in hBMSCs following exposure to aminobisphosphonates. Further analysis including Western blotting and loss-of-function studies revealed osteopontin as having a negative influence on the mineralization of differentiating osteoporotic bone-forming cells. CONCLUSIONS:The results presented here demonstrate for the first time that aminobisphosphonate treatment of osteoporotic hBMSCs enhances their capacity for osteoblast formation and subsequent mineral deposition, thus supporting the concept of aminobisphosphonates as having an osteoanabolic effect in osteoporosis. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 ConclusionsThe results presented here demonstrate for the first time that aminobisphosphonate treatment of osteoporotic hBMSCs enhances their capacity for osteoblast formation and subsequent mineral deposition, thus supporting the concept of aminobisphosphonates as having an osteoanabolic effect in osteoporosis.Keywords: Osteoporosis; Aminobisphosphonate; Bone marrow stromal cell; Osteogenic differentiation; mineralization. Mini AbstractIn the present study, we evaluated the potential for aminobisphosphonates...

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Abnormalities of Insulin-Like Growth Factor-I Signaling and Impaired Cell Proliferation in Osteoblasts from Subjects with Osteoporosis

Cited by 45 publications

References 48 publications

Osteoblasts with impaired spreading capacity benefit from the positive charges of plasma polymerised allylamine

Osteoblasts with impaired spreading capacity benefit from the positive charges of plasma polymerised allylamine

Low-intensity Ultrasound Increases FAK, ERK-1/2, and IRS-1 Expression of Intact Rat Bones in a Noncumulative Manner

Osteoanabolic effect of alendronate and zoledronate on bone marrow stromal cells (BMSCs) isolated from aged female osteoporotic patients and its implications for their mode of action in the treatment of age-related bone loss

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