Disruption of insulin-like growth factor-I expression in type IIαI collagen-expressing cells reduces bone length and width in mice

Govoni, Kristen E; Lee, Seong Keun; Chung, Yoon‐Sok; Behringer, Richard R.; Wergedal, Jon E.; Baylink, David J.; Mohan, Subburaman

doi:10.1152/physiolgenomics.00022.2007

Cited by 95 publications

(97 citation statements)

References 64 publications

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“…The results revealed that loss of IGF-1 produced by these collagen2-expressing chondrocytes led to changes in the longitudinal growth and width of bone as well as a decrease in bone mineral density. 32 Although the width and the length of the femurs are smaller in the conditional knockouts, no effect was reported on the organization of the growth plate. The IGF1R has been deleted using the Col2a1, and its phenotype shows growth plate defects including disorganized chondrocytes, decreased proliferation and increased apoptosis.…”

Section: Igf-1 and Chondrocytesmentioning

confidence: 99%

IGF-1 regulation of key signaling pathways in bone

2013

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Insulin-like growth factor 1 (IGF-1) is an unique peptide that functions in an endocrine/paracrine and autocrine manner in most tissues. Although it was postulated initially that liver-derived IGF-1 was the major source of IGF-1 (that is, the somatomedin hypothesis), it is also produced in a wide variety of tissues and can function in numerous ways as both a proliferative and differentiative factor. One such tissue is bone and all cell lineages in the skeleton have been shown to not only require IGF-1 for normal development and function but also to respond to IGF-1 via the IGF-1 receptor. Ligandreceptor activation leads to several distinct downstream signaling cascades, which have significant implications for cell survival, protein synthesis and energy utilization. The novel role of IGF-1 in regulating metabolic demands of the bone remodeling unit is currently under investigation. More studies are likely to shed new light on various aspects of skeletal physiology and potentially may lead to new therapeutics.

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Section: Igf-1 and Chondrocytesmentioning

confidence: 99%

IGF-1 regulation of key signaling pathways in bone

2013

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“…(29) These mice display a cartilage-specific Cre expression and have the capacity to recombine loxP-flanked DNA sequences in a cartilage-specific manner. (29,30) Studies using reporter mice have demonstrated that the Col2a1-Cre mice cause a specific recombination in cartilage not only in the appendicular but also in the axial skeleton. (29) To analyze the expression pattern of Cre recombinase in Col2a1-Cre transgenic mice, we used the ROSA26-Cre reporter mouse strain R26R.…”

Section: Reporter Micementioning

confidence: 99%

“…(29,30) To validate that the Col2a1-Cre mouse strain has the capacity to specifically recombine DNA in chondrocytes postnatally, we mated Col2a1-Cre mice with ROSA26-Cre reporter mice. Humerus and liver of 4-week-old offspring were stained with X-gal to detect b-galactosidase activity.…”

Section: Cartilage-specific Inactivation Of Eramentioning

confidence: 99%

The role of estrogen receptor α in growth plate cartilage for longitudinal bone growth

Börjesson

Lagerquist

Liu

et al. 2010

Journal of Bone and Mineral Research

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Estrogens enhance skeletal growth during early sexual maturation, whereas high estradiol levels during late puberty result in growth plate fusion in humans. Although the growth plates do not fuse directly after sexual maturation in rodents, a reduction in growth plate height is seen by treatment with a high dose of estradiol. It is unknown whether the effects of estrogens on skeletal growth are mediated directly via estrogen receptors (ERs) in growth plate cartilage and/or indirectly via other mechanisms such as the growth hormone/ insulin-like growth factor 1 (GH/IGF-1) axis. To determine the role of ERa in growth plate cartilage for skeletal growth, we developed a mouse model with cartilage-specific inactivation of ERa. Although mice with total ERa inactivation displayed affected longitudinal bone growth associated with alterations in the GH/IGF-1 axis, the skeletal growth was normal during sexual maturation in mice with cartilagespecific ERa inactivation. High-dose estradiol treatment of adult mice reduced the growth plate height as a consequence of attenuated proliferation of growth plate chondrocytes in control mice but not in cartilage-specific ERa À/À mice. Adult cartilage-specific ERa À/À mice continued to grow after 4 months of age, whereas growth was limited in control mice, resulting in increased femur length in 1-year-old cartilage-specific ERa À/À mice compared with control mice. We conclude that during early sexual maturation, ERa in growth plate cartilage is not important for skeletal growth. In contrast, it is essential for high-dose estradiol to reduce the growth plate height in adult mice and for reduction of longitudinal bone growth in elderly mice. ß

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“…(7,8) Not only serum IGF-1 but also locally produced IGF-1 in bone is required for the achievement of normal peak bone mass, as demonstrated by the reduced bone mass in mouse models with osteoblast/chondrocyte-specific IGF-1 inactivation. (9,10) Patients with growth hormone deficiency (GHD) or GH insensitivity have low serum IGF-1 and reduced bone mineral density (BMD), and GH treatment of patients with GHD results in improved bone mass associated with increased serum IGF-1. (1)(2)(3)11) A role of IGF-1 in bone metabolism is supported by the fact that patients with IGF deficiency as a result of IGF1 gene deletion or inactivating mutation display osteopenia.…”

Section: Introductionmentioning

confidence: 99%

Older men with low serum IGF-1 have an increased risk of incident fractures: The MrOS Sweden study

Ohlsson

Mellström

Carlzon

et al. 2010

Journal of Bone and Mineral Research

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Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Insulin-like growth factor 1 (IGF-1) is a key determinant of bone mass, but the association between serum IGF-1 and incident fractures in men remains unclear. To determine the predictive value of serum IGF-1 for fracture risk in men, older men (n ¼ 2902, mean age of 75 years) participating in the prospective, population-based Osteoporotic Fractures in Men (MrOS) Sweden study were followed for a mean of 3.3 years. Serum IGF-1 was measured at baseline by radioimmunoassay. Fractures occurring after the baseline visit were validated. In age-adjusted hazards regression analyses, serum IGF-1 associated inversely with risk of all fractures [hazard ratio (HR) per SD decrease ¼ 1.23, 95% confidence interval (CI) 1.07-1.41], hip fractures (HR per SD decrease ¼ 1.45, 95% CI 1.07-1.97), and clinical vertebral fractures (HR per SD decrease ¼ 1.40, 95% CI 1.10-1-78). The predictive role of serum IGF-1 for fracture risk was unaffected by adjustment for height, weight, prevalent fractures, falls, and major prevalent diseases. Further adjustment for bone mineral density (BMD) resulted in an attenuated but still significant association between serum IGF-1 and fracture risk. Serum IGF-1 below but not above the median was inversely related to fracture incidence. The population-attributable risk proportion was 7.5% for all fractures and 22.9% for hip fractures. Taken together, older men with low serum IGF-1 have an increased fracture risk, especially for the two most important fracture types, hip and vertebral fractures. The association between serum IGF-1 and fracture risk is partly mediated via BMD. ß

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Disruption of insulin-like growth factor-I expression in type IIαI collagen-expressing cells reduces bone length and width in mice

Cited by 95 publications

References 64 publications

IGF-1 regulation of key signaling pathways in bone

IGF-1 regulation of key signaling pathways in bone

The role of estrogen receptor α in growth plate cartilage for longitudinal bone growth

Older men with low serum IGF-1 have an increased risk of incident fractures: The MrOS Sweden study

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