IGF-I secreted by osteoblasts acts as a potent chemotactic factor for osteoblasts

Nakasaki, Manando; Yoshioka, Kiyoko; Miyamoto, Yasuhide; Sasaki, Takehiko; Yoshikawa, Hideki; Itoh, Kazuyuki

doi:10.1016/j.bone.2008.07.241

Cited by 73 publications

(65 citation statements)

References 43 publications

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“…We have previously shown that TGFβ1 is activated during bone resorption and induces migration of MSCs from their quiescent phase and that IGF-1 released from bone matrix stimulates their osteoblast differentiation. However, several in vitro studies have suggested that IGF-1 may have a role in MSC migration as well (22)(23)(24)(25). To clarify the specific role of IGF-1 on MSC function, in the current study, we further investigated the role of IGF-1 in MSCs during osteoblast differentiation using conditional knockout of IGF1R in the Nestin + MSCs.…”

Section: Discussionmentioning

confidence: 97%

“…IGF-1 signaling has been implicated to play a role in both MSC migration and differentiation (20,(22)(23)(24)(25). Therefore, to assess migration and differentiation of MSCs, we quantified the number of osteoprogenitors and mature osteoblasts by bone perimeter.…”

Section: Igf-1 Is Necessary For Msc Differentiation Not Recruitment mentioning

confidence: 99%

“…Others have found that IGF-1 signaling in mature osteoblasts enhances the function of the mature osteoblast (21). Data has also implicated IGF-1 as a mitogenic factor for MSCs in culture (22)(23)(24)(25). However, as multiple other cytokines and growth factors stimulate similar cell signaling pathways, the contribution of IGF-1 signaling in vivo to MSC cell migration remains unknown.…”

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IGF-1 Signaling is Essential for Differentiation of Mesenchymal Stem Cells for Peak Bone Mass

et al. 2013

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Survival of children with chronic medical illnesses is leading to an increase in secondary osteoporosis due to impaired peak bone mass (PBM). Insulin-like growth factor type 1 (IGF-1) levels correlate with the pattern of bone mass accrual and many chronic illnesses are associated with low IGF-1 levels. Reduced serum levels of IGF-1 minimally affect the integrity of the skeleton, whereas recent studies suggest that skeletal IGF-I regulates PBM. To determine the role of IGF-1 in postnatal bone mass accrual regardless of source, we established an inducible type 1 Igf receptor Cre/lox knockout mouse model, in which the type 1 Igf receptor was deleted inducibely in the mesenchymal stem cells (MSCs) from 3-7 weeks of age. The size of the mouse was not affected as knockout and wild type mice had similar body weights and nasoanal and femoral lengths. However, bone volume and trabecular bone thickness were decreased in the secondary spongiosa of female knockout mice relative to wild type controls, indicating that IGF-1 is critical for bone mass. IGF-1 signaling in MSCs in vitro has been implicated to be involved in both migration to the bone surface and differentiation into bone forming osteoblasts. To clarify the exact role of IGF-1 in bone, we found by immunohistochemical analysis that a similar number of Osterix-positive osteoprogenitors were on the bone perimeter, indicating migration of MSCs was not affected. Most importantly, 56% fewer osteocalcin-positive mature osteoblasts were present on the bone perimeter in the secondary spongiosa in knockout mice versus wild type littermates. These in vivo data demonstrate that the primary role of skeletal IGF-1 is for the terminal differentiation of osteoprogenitors, but refute the role of IGF-1 in MSC migration in vivo. Additionally, these findings confirm that impaired IGF-1 signaling in bone MSCs is sufficient to impair bone mass acquisition. Keywords: osteoblasts; knockout mice; cell migration; IGF receptor; nestin Bone Research (2013) 2: 186-194. doi: 10.4248 /BR201302007 IntroductionBone mass normally peaks in mid to late adolescence, plateaus for several years and then declines over time (1-5). Acquisition of a higher peak bone mass (PBM) in adolescence is associated with reduced subsequent fracture risk, whereas impaired acquisition of PBM or loss of bone in childhood is associated with greater fracture risk. Chronic illness in childhood impairs PBM acquisition. Survival of many chronic illnesses in childhood are leading to a growing incidence of secondary osteoporosis (6). The prevention of secondary osteoporosis in children with chronic illnesses depends on protecting the bones of this at-risk population. However, before treatment can be developed, the regulation of cellular signaling mechanisms involved in the acquisition of bone mass needs to be further elucidated.Janet L. Crane et al. www.boneresearch.org | Bone Research 187The only cells that form new bone are osteoblasts, which are non-replicative mononuclear cells derived from mesenchymal stem cells (MSC) (7-...

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Section: Discussionmentioning

confidence: 97%

Section: Igf-1 Is Necessary For Msc Differentiation Not Recruitment mentioning

confidence: 99%

mentioning

confidence: 99%

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IGF-1 Signaling is Essential for Differentiation of Mesenchymal Stem Cells for Peak Bone Mass

et al. 2013

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“…The plateletderived growth factor β (PDGF-BB) was found to be a very potent chemotactic factor for MSC, primary osteoblasts and osteoblastic cell lines (5)(6)(7)(8)(9)(10). Further examples are the insulinlike growth factors 1 (IGF-1) and 2 (IGF-2), which stimulate the site-directed migration of MSC and osteoblasts (5,11,12). In addition to its known angiogenic effects, vascular endothelial growth factor A (VEGF-A) was found to have a dose-dependent chemotactic effect on MSC and primary human osteoblasts, in vitro, that is mediated through VEGF receptor 1 activation (13,14).…”

Section: Introductionmentioning

confidence: 99%

IL-1β Inhibits Human Osteoblast Migration

Hengartner

Fiedler

Ignatius

et al. 2013

Mol Med

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Bone has a high capacity for self-renewal and repair. Prolonged local secretion of interleukin 1β (IL-1β), however, is known to be associated with severe bone loss and delayed fracture healing. Since induction of bone resorption by IL-1β may not sufficiently explain these pathologic processes, we investigated, in vitro, if and how IL-1β affects migration of multipotent mesenchymal stromal cells (MSC) or osteoblasts. We found that homogenous exposure to IL-1β significantly diminished both nondirectional migration and site-directed migration toward the chemotactic factors platelet-derived growth factor (PDGF)-BB and insulinlike growth factor 1 (IGF-1) in osteoblasts. Exposure to a concentration gradient of IL-1β induced an even stronger inhibition of migration and completely abolished the migratory response of osteoblasts toward PDGF-BB, IGF-1, vascular endothelial growth factor A (VEGF-A) and the complement factor C5a. IL-1β induced extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinases (JNK) activation and inhibition of these signaling pathways suggested an involvement in the IL-1β effects on osteoblast migration. In contrast, basal migration of MSC and their migratory activity toward PDGF-BB was found to be unaffected by IL-1β. These results indicate that the presence of IL-1β leads to impaired recruitment of osteoblasts which might influence early stages of fracture healing and could have pathological relevance for bone remodeling in inflammatory bone disease.

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“…Four of them have never before been found in the circulation: Transforming growth factor -induced protein ig-h3 ( ig-h3), cartilage acidic protein 1 (CRTAC1), procollagen C proteinase enhancer protein (PCPE-1) and TGF-receptor type 3 (TGF--R-3). Nakasaki et al (2008) have identified insulin-like growth factor I(IGF-I) as potent chemotactic factor for osteoblasts and showed IGF-I involvement in fracture healing. They used five step sequential chromatography to purify IGF-I from 18 L of MC3T3-E1 (mouse osteoblast-like cell line) serum free conditioned media (CM).…”

Section: Bone and Cartilagementioning

confidence: 99%

The Use of Mass Spectrometry in Characterization of Bone Morphogenetic Proteins from Biological Samples

Razdorov¹,

Vukičević²

2012

Tandem Mass Spectrometry - Applications and Principles

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IGF-I secreted by osteoblasts acts as a potent chemotactic factor for osteoblasts

Cited by 73 publications

References 43 publications

IGF-1 Signaling is Essential for Differentiation of Mesenchymal Stem Cells for Peak Bone Mass

IGF-1 Signaling is Essential for Differentiation of Mesenchymal Stem Cells for Peak Bone Mass

IL-1β Inhibits Human Osteoblast Migration

The Use of Mass Spectrometry in Characterization of Bone Morphogenetic Proteins from Biological Samples

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