Irisin Enhances Osteoblast Differentiation<i>In Vitro</i>

Colaianni, Graziana; Cuscito, Concetta; Mongelli, Teresa; Oranger, Angela; Mori, Giorgio; Brunetti, Giacomina; Colucci, Silvia; Cinti, Saverio; Grano, Maria

doi:10.1155/2014/902186

Cited by 176 publications

(157 citation statements)

References 31 publications

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“…We have previously reported that conditioned medium from cultures of myoblasts harvested from mice postexercise was able to enhance osteoblast differentiation in vitro (17). This observation suggested that the newly discovered myokine irisin could be a potential candidate for muscle-osteoblast connectivity.…”

Section: Resultsmentioning

confidence: 94%

“…We have shown previously that myokine-enriched medium from myoblast cultures was able to enhance the differentiation of bone marrow stromal cells into mature, bone-forming osteoblasts in vitro (17). Here, we demonstrate that recombinant irisin (r-irisin), when injected into mice, increases cortical bone mass and strength.…”

mentioning

confidence: 71%

“…The threepoint bending test was carried out according to a previous protocol (54). Primary osteoblast culture, immunoblotting and qPCR were performed as described (17). Cfu-f and Cfu-ob were determined by alkaline phosphatase (day 10) and von Kossa (day 21) labeling, respectively.…”

Section: Methodsmentioning

confidence: 99%

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The myokine irisin increases cortical bone mass

Colaianni

Cuscito

Mongelli

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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It is unclear how physical activity stimulates new bone synthesis. We explored whether irisin, a newly discovered myokine released upon physical activity, displays anabolic actions on the skeleton. Young male mice were injected with vehicle or recombinant irisin (r-irisin) at a low cumulative weekly dose of 100 µg kg(-1). We observed significant increases in cortical bone mass and strength, notably in cortical tissue mineral density, periosteal circumference, polar moment of inertia, and bending strength. This anabolic action was mediated primarily through the stimulation of bone formation, but with parallel notable reductions in osteoclast numbers. The trabecular compartment of the same bones was spared, as were vertebrae from the same mice. Higher irisin doses (3,500 µg kg(-1) per week) cause browning of adipose tissue; this was not seen with low-dose r-irisin. Expectedly, low-dose r-irisin modulated the skeletal genes, Opn and Sost, but not Ucp1 or Pparγ expression in white adipose tissue. In bone marrow stromal cell cultures, r-irisin rapidly phosphorylated Erk, and up-regulated Atf4, Runx2, Osx, Lrp5, β-catenin, Alp, and Col1a1; this is consistent with a direct receptor-mediated action to stimulate osteogenesis. We also noted that, although the irisin precursor Fndc5 was expressed abundantly in skeletal muscle, other sites, such as bone and brain, also expressed Fndc5, albeit at low levels. Furthermore, muscle fibers from r-irisin-injected mice displayed enhanced Fndc5 positivity, and irisin induced Fdnc5 mRNA expression in cultured myoblasts. Our data therefore highlight a previously unknown action of the myokine irisin, which may be the molecular entity responsible for muscle-bone connectivity

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Section: Resultsmentioning

confidence: 94%

mentioning

confidence: 71%

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The myokine irisin increases cortical bone mass

Colaianni

Cuscito

Mongelli

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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386

356

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“…20 More recently, the key evidence of a direct action of Irisin on bone has emerged by in vivo studies demonstrating that a low dose of recombinant Irisin (r-Irisin), which has no effect on fat, improves cortical bone mass and bone strength. We showed that tibiae of young male mice treated with r-Irisin exhibited a þ 7.15% increase in cortical BMD compared with those of mice injected with vehicle.…”

Section: Irisin the Messenger Of Healthy Bone-muscle Unitmentioning

confidence: 99%

Role of Irisin on the bone–muscle functional unit

Colaianni

Grano

2015

BoneKEy Reports

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Irisin was originally recognized as a hormone-like myokine secreted as a product of fibronectin type III domain containing 5 from skeletal muscle in response to exercise both in mice and humans. The first role attributed to Irisin was its ability to induce trans-differentiation of white adipose tissue into brown, but we recently demonstrated that Irisin also has a central role in the control of bone mass, even at lower concentration than required to induce the browning response. Considering how physical exercise is important for the development of an efficient load-bearing skeleton, we can now consider this myokine as one of the molecules responsible for the positive correlation between exercise and healthy bone, linking to the well-established relationship between muscle and bone. Recombinant Irisin (r-Irisin), administered at low dose in young mice, increases cortical bone mineral density and positively modifies bone geometry. Irisin exerts its effect prevalently on osteoblast lineage by enhancing differentiation and activity of bone-forming cells, through the increase in activating transcription factor 4 expression. Low-dose r-Irisin also increases osteopontin and decreases sclerostin synthesis but did not affect Uncoupling protein 1 expression in white adipose tissue, whose upregulation is known to cause browning of fat, when Irisin is administered at a higher dose. These findings offer an explanation to the positive outcome on the skeleton triggered by skeletal muscle during physical activity and prove that the bone tissue is more sensitive than the adipose tissue to the Irisin action.

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“…3,7,and 8), whereas data with nonnormal distribution were compared by nonparametric Mann-Whitney test (i.e., Figs. 1,2,4,5,6,and 9). Two-way ANOVA was used to determine how the BMD outcome was affected by sex (male vs. female) and genotype (wild-type vs. BKO).…”

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confidence: 99%

Running exercise alleviates trabecular bone loss and osteopenia in hemizygous β-globin knockout thalassemic mice

Thongchote

Svasti

Teerapornpuntakit

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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Thongchote K, Svasti S, Teerapornpuntakit J, Krishnamra N, Charoenphandhu N. Running exercise alleviates trabecular bone loss and osteopenia in hemizygous ␤-globin knockout thalassemic mice. Am J Physiol Endocrinol Metab 306: E1406 -E1417, 2014. First published April 29, 2014; doi:10.1152/ajpendo.00111.2014.-A marked decrease in ␤-globin production led to ␤-thalassemia, a hereditary anemic disease associated with bone marrow expansion, bone erosion, and osteoporosis. Herein, we aimed to investigate changes in bone mineral density (BMD) and trabecular microstructure in hemizygous ␤-globin knockout thalassemic (BKO) mice and to determine whether endurance running (60 min/day, 5 days/wk for 12 wk in running wheels) could effectively alleviate bone loss in BKO mice. Both male and female BKO mice (1-2 mo old) showed growth retardation as indicated by smaller body weight and femoral length than their wild-type littermates. A decrease in BMD was more severe in female than in male BKO mice. Bone histomorphometry revealed that BKO mice had decreases in trabecular bone volume, trabecular number, and trabecular thickness, presumably due to suppression of osteoblast-mediated bone formation and activation of osteoclast-mediated bone resorption, the latter of which was consistent with elevated serum levels of osteoclastogenic cytokines IL-1␣ and -1␤. As determined by peripheral quantitative computed tomography, running increased cortical density and thickness in the femoral and tibial diaphyses of BKO mice compared with those of sedentary BKO mice. Several histomorphometric parameters suggested an enhancement of bone formation (e.g., increased mineral apposition rate) and suppression of bone resorption (e.g., decreased osteoclast surface), which led to increases in trabecular bone volume and trabecular thickness in running BKO mice. In conclusion, BKO mice exhibited pervasive osteopenia and impaired bone microstructure, whereas running exercise appeared to be an effective intervention in alleviating bone microstructural defect in ␤-thalassemia. bone histomorphometry; bone mineral density; endurance exercise; running wheel; osteoporosis HEMOGLOBIN-OXYGEN-CARRYING METALLOPROTEIN in the erythrocytes-is composed of two ␣-globin chains and two ␤-globin chains. Inadequate production or absence of ␤-globin is found in a hereditary disease known as ␤-thalassemia, which is a common autosomal recessive anemic disorder in several populations, such as Chinese, Southeast Asian, and Mediterranean populations (6,15,34,59). Thalassemic patients and rodents both manifest ineffective erythropoiesis, extramedullary erythropoiesis, splenomegaly, iron overload, growth retardation, short stature, and skeletal deformity (16,28,31,38,43,56,62). However, little is known regarding the detailed changes in bone mineral density (BMD) and microstructural defect as well as the cellular mechanism of bone loss, especially at the early stages of the disease in young growing and adolescent mice.Our recent study has provided evidence that defective bone matrix ...

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Irisin Enhances Osteoblast DifferentiationIn Vitro

Cited by 176 publications

References 31 publications

The myokine irisin increases cortical bone mass

The myokine irisin increases cortical bone mass

Role of Irisin on the bone–muscle functional unit

Running exercise alleviates trabecular bone loss and osteopenia in hemizygous β-globin knockout thalassemic mice

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