Colaianni et al., 20151313 Colaianni G, Cuscito C, Mongelli T, Pignataro P, Buccoliero C, Liu P, et al. The myokine irisin increases cortical bone mass. Proc Natl Acad Sci USA. 2015 Sep;112(39):12157-62. https://doi.org/10.1073/pnas.1516622112 https://doi.org/10.1073/pnas.1516622112...
|
C57BL/6 |
Control group |
Dynamic histomorphometry |
Not performed |
r-irisin 100μg/kg i.p. |
Unpaired Student’s t test |
r-irisin increased radiodensity of femora and tibia; cortical tissue mineral density (C-TMD) and tibial cortical bone surface |
Intermittent |
Male mice |
vehicle |
µCT |
Once a week (4 weeks) |
No effect on trabecular bone |
2 months old |
n = 4-5 |
X-ray from femur and tibia |
|
r-irisin increased the three-point bending test and force at peak; bone formation rate (BFR) and mineral apposition rate (MFR) |
|
|
|
|
r-irisin increased osteoblasts and decreased osteoclasts |
|
r-irisin group |
|
|
|
|
n = 4-5 |
|
|
|
Kim et al., 20151515 Kim HJ, So B, Choi M, Kang D, Song W. Resistance exercise training increases the expression of irisin concomitant with improvement of muscle function in aging mice and humans. Exp Gerontol. 2015 Oct;70:11-7. https://doi.org/10.1016/j.exger.2015.07.006 https://doi.org/10.1016/j.exger.2015.07....
|
C57BL/6 |
Control group |
Dual energy X-ray absorptiometry (DXA) |
Resistance ladder climbing |
Serum irisin quantification |
Independent t test |
Exercise increased serum irisin levels and soleus skeletal muscle extract. |
Intermittent |
Male mice |
n = 6 |
3 days/week |
Irisin quantification in skeletal muscles extracts (ELISA) |
No significant difference in Bone mineral contents or Bone mineral density when compared with control group. |
19 months old |
|
8 weeks |
|
|
|
Resistance exercise group |
|
|
|
|
n = 7 |
|
|
|
Colaianni et al., 20171919 Colaianni G, Mongelli T, Cuscito C, Pignataro P, Lippo L, Spiro G, et al. Irisin prevents and restores bone loss and muscle atrophy in hind-limb suspended mice. Sci Rep. 2017 Jun;7(1):2811. https://doi.org/10.1038/s41598-017-02557-8 https://doi.org/10.1038/s41598-017-02557...
|
C57BL6 |
Control groups – not suspended (n= 8): |
µCT and Contact radiography |
Not performed. |
Vehicle (physiologic water sterilized by 0.22 μ filtration) |
One-way analysis of variance (ANOVA) with Bonferroni’s post hoc test. |
Preventive Protocol |
Intermittent |
Male mice |
vehicle |
Histological analysis |
r-irisin 100μg/kg i.p. once a week for 4 weeks |
HLS decreased both cortical and trabecular BMD and trabecular BV/TV of femur |
2 months old |
r-irisin |
RT-PCR |
Preventive protocol: Once a week (4 weeks) during HLS |
r-irisin prevented and recovered (curative protocol) both cortical and trabecular BMD and BV/TV |
|
|
Western Blot |
Curative protocol: after 4 weeks of HLS |
r-irisin treatment did not altered trabecular BMD and BV/TV of femur in animals not submitted to HLS. |
Colaianni et al., 20171919 Colaianni G, Mongelli T, Cuscito C, Pignataro P, Lippo L, Spiro G, et al. Irisin prevents and restores bone loss and muscle atrophy in hind-limb suspended mice. Sci Rep. 2017 Jun;7(1):2811. https://doi.org/10.1038/s41598-017-02557-8 https://doi.org/10.1038/s41598-017-02557...
|
|
Hindlimb suspended (HLS) preventive groups (n = 8): |
Ex vivo primary cell cultures |
Not performed. |
|
One-way analysis of variance (ANOVA) with Bonferroni’s post hoc test. |
|
Intermittent |
|
vehicle |
|
|
|
|
r-irisin |
|
|
|
|
HLS curative groups (n = 8): |
|
|
|
|
vehicle |
|
|
|
|
r-irisin |
|
|
|
|
reload+ vehicle |
|
|
|
|
rest vehicle+
|
|
|
|
|
Treatment after 4 weeks of HLS |
|
|
|
|
+ not HLS |
|
|
|
Zhang et al., 20171616 Zhang J, Valverde P, Zhu X, Murray D, Wu Y, Yu L, et al. Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism. Bone Res. 2017 Feb;5(1):16056. https://doi.org/10.1038/boneres.2016.56 https://doi.org/10.1038/boneres.2016.56...
|
C57BL/6J |
Control group: empty cages for two weeks (n = 18). |
μCT |
Voluntary exercise in polycarbonate running wheel |
r-irisin 3.24 ng i.p. daily for two weeks. |
One-way ANOVA |
Two weeks of voluntary wheel-running exercise increased FNDC5 and PGC1α mRNA levels in bone tissue |
Continuous |
APN-KO |
Exercise group: voluntary wheel running for two weeks (n = 18). |
Histology and immunohistochemical staining protocols |
2 weeks |
Lentiviral FNDC5, Control EGFP, FNDC5 shRNA lentivirus and scramble shRNA lentivirus i.p. (4×1088 Brotto M, Bonewald L. Bone and muscle: interactions beyond mechanical. Bone. 2015 Nov;80:109-14. https://doi.org/10.1016/j.bone.2015.02.010 https://doi.org/10.1016/j.bone.2015.02.0...
transducing units per mice) daily for four or two weeks |
Protein expression of FNDC5 and irisin increased over sixfold in bone tissue after exercise |
Male mice |
r-irisin for two weeks (n =6) |
Bone marrow used for western blot and RT-PCR analysis |
|
|
r-irisin significantly increased μCT bone volume/total volume, trabecular thickness, and cortical thickness compared with the saline-treated group (μCT analyses only for r-irisin groups versus control. Exercise effects not investigated by μCT). |
5 weeks old |
Saline for two weeks (n=6) |
ELISA |
|
|
The lentiviral injections of FNDC5 in APN-KO mice significantly increased FNDC5 mRNA expression in bone |
|
Lentiviral FNDC5 for four weeks (n=5). |
|
|
|
|
Zhang et al., 20171616 Zhang J, Valverde P, Zhu X, Murray D, Wu Y, Yu L, et al. Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism. Bone Res. 2017 Feb;5(1):16056. https://doi.org/10.1038/boneres.2016.56 https://doi.org/10.1038/boneres.2016.56...
|
APN-KO |
Control EGFP (n=5). |
|
|
|
One-way ANOVA |
|
Continuous |
Male mice |
FNDC5 shRNA lentivirus + wheel running two weeks (n = 5). |
|
|
|
|
5 weeks old |
Scramble shRNA lentivirus + wheel running two weeks (n =5). |
|
|
|
|
Kim et al., 20181212 Kim H, Wrann CD, Jedrychowski M, Vidoni S, Kitase Y, Nagano K, et al. Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors. Cell. 2018 Dec;175(7):1756-1768.e17. https://doi.org/10.1016/j.cell.2018.10.025 https://doi.org/10.1016/j.cell.2018.10.0...
|
C57BL/6J |
9-month-old female mice for OVX experiment and analysis of vertebrae and femurs |
Bone histomorphometric analysis |
Not performed. |
r-irisin 1mg/kg/day i. p. for 6 days. |
Two-way ANOVA |
FNDC5 null mice had a significantly lower level of RANKL mRNA in whole bones both in males and females, whereas OPG was not altered. |
Continuous |
|
5-month-old female mice used for μCT analysis of femurs and gene expression analysis of tibia |
μCT |
Unpaired Student’s t test |
FNDC5 null mice had significantly higher femoral trabecular bone mass and greater connectivity density than wild-type mice |
FNDC5 KO |
8-week-old C57BL/6J wild-type female mice euthanized after 2 weeks of OVX to measure irisin level in plasma |
RT-PCR |
|
r-irisin raised the sclerostin mRNA level in osteocyte-enriched bones in vivo. |
|
8-week-old C57BL/6J wild-type male mice were used for irisin injection experiments |
West |
|
|
8 weeks to 9 months old |
(n = 4-7 animals per group) |
Quantitative Proteomic analysis |
|
|
|
|
Ex vivo cell cultures |
|
|
Kim et al., 20181212 Kim H, Wrann CD, Jedrychowski M, Vidoni S, Kitase Y, Nagano K, et al. Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors. Cell. 2018 Dec;175(7):1756-1768.e17. https://doi.org/10.1016/j.cell.2018.10.025 https://doi.org/10.1016/j.cell.2018.10.0...
|
Male and female mice |
|
|
Not performed. |
r-irisin 1mg/kg/day i. p. for 6 days. |
|
|
Continuous |
Narayanan et al., 20181717 Narayanan SA, Metzger CE, Bloomfield SA, Zawieja DC. Inflammation-induced lymphatic architecture and bone turnover changes are ameliorated by irisin treatment in chronic inflammatory bowel disease. FASEB J. 2018 Sep;32(9):4848-61. https://doi.org/10.1096/fj.201800178R https://doi.org/10.1096/fj.201800178R...
|
Sprague-Dawley rats |
Control -vehicle - group (n = 8). |
Static and dynamic histomorphometry of proximal tibia and lumbar vertebrae relative mineralized bone surface, mineral apposition rate, and bone formation rate; and identification of osteoclast and osteoid surfaces |
Not performed. |
r- irisin i.p. (18 ng/ml injections) 2 times/week (3.5 d apart) for 3 weeks. |
Two-way ANOVA (2x2 factorial scheme) |
r-irisin decreased osteoclast surface and increased osteoid surface and bone formation rate. |
Intermittent |
|
Vehicle + r-irisin group (n = 8). |
Immunohistochemistry of distal femur osteocyte proteins (TNF- α, IL–6, IL-10, IL-4, annexin V, sclerostin, RANKL and OPG). |
IBD caused an increase in osteocytes positive for TNF-α, IL-6, sclerostin and osteoclastogenesis regulators RANKL and OPG. Additionally, osteocyte apoptosis, as measured by annexin V, was elevated in IBD. r-irisin treatment lowered these factors to levels at or lower than vehicle. |
Male |
Inflammatory bowel disease (IBD) group (n = 8). |
|
|
|
Inflammatory bowel disease (IBD) + r-irisin group (n = 8). |
|
|
2-months old |
|
|
|
Kang et al., 20191414 Kang YS, Kim JC, Kim JS, Kim SH. Effects of swimming exercise on serum irisin and bone FNDC5 in rat models of high-fat diet-induced osteoporosis. J Sports Sci Med. 2019 Nov;18(4):596-603.
|
prague-Dawley rats. |
Control diet group (n = 10). |
BMD and microstructure of femur and tibia via µCT. |
8 weeks of low-intensity swimming exercise initiated with 45 min/day for the first two weeks and 60 min/day for the last six weeks. |
Serum irisin levels were measured using ELISA kits. |
Independent t test |
8 weeks of swimming exercise improved obesity, BMD, bone microstructure and bone metabolic factors. |
Continuous |
|
High fat diet (HFD) induced osteoporosis (8 weeks) group (n = 10). |
Osteocalcin, CTX-1 and irisin levels in the blood |
One-way ANOVA |
Irisin levels in the blood and the expressions of FNDC5 and PGC-1α in the bone were significantly lower in the HFD group than in the CD group, but higher in the swimming group than in the HFD group. |
Kang et al., 20191414 Kang YS, Kim JC, Kim JS, Kim SH. Effects of swimming exercise on serum irisin and bone FNDC5 in rat models of high-fat diet-induced osteoporosis. J Sports Sci Med. 2019 Nov;18(4):596-603.
|
Male |
High fat diet (HFD) induced osteoporosis (8 weeks) + swimming exercise (further 8 weeks) group (n = 10). |
Immunohistochemistry of femur IL-1, β-catenin, PGC-1α and FNDC5 in the tibia and femur |
8 weeks of low-intensity swimming exercise initiated with 45 min/day for the first two weeks and 60 min/day for the last six weeks. |
Serum irisin levels were measured using ELISA kits. |
|
Swimming exercise reduced HFD-induced IL-1 and increased β-catenin, FNDC5, and PGC-1α in bone. |
Continuous |
8 weeks old |
|
|
|
|
Metzger et al., 20193636 Zhao R, Zhou Y, Li J, Lin J, Cui W, Peng Y, et al. Irisin regulating skeletal response to endurance exercise in ovariectomized mice by promoting Akt/β-Catenin Pathway. Front Physiol. 2021 Mar;12:639066. https://doi.org/10.3389/fphys.2021.639066 https://doi.org/10.3389/fphys.2021.63906...
|
Sprague-Dawley rats |
Control group (n = 8). |
Volumetric BMD on the proximal tibia and femoral neck and L4 |
Not performed |
r- irisin i.p. (18 ng/ml injections) 2 times/week (3.5 d apart) for 3 weeks. |
2 x 2 factorial ANOVA |
Animals induced to inflammatory bowel disease showed lower bone mineral density and higher osteocyte pro-inflammatory cytokines. |
Intermittent |
|
Control + irisin (n = 8). |
Three-point bend test was conducted at the tibia midshaft and compression test at the femoral neck |
Cancellous vBMD was not different among the four groups |
Male |
Inflammatory bowel disease (IBD) induced by dextran sodium sulfate (n =8). |
Dynamic and static histomorphometry and bone immunohistochemistry (TNF-α, IL-6, RANKL, OPG, sclerostin and annexin V) and bone formation rate. |
r-irisin treatment ameliorated bone inflammatory profile but did not alter bone mineral loss. |
|
Inflammatory bowel disease (IBD) induced by dextran sodium sulfate + irisin (n = 8). |
|
r-irisin treatment mitigated declines in osteoid surface and restored IBD animals osteoclast surfaces to control levels |
8 weeks old |
|
|
r-irisin treatment improved bone formation rate without modifying BMD. |
|
|
|
r-irisin treatment in IBD rats mitigated the increase in TNF-α, IL-6, RANKL, OPG, sclerostin and annexin V |
Metzger et al., 20193636 Zhao R, Zhou Y, Li J, Lin J, Cui W, Peng Y, et al. Irisin regulating skeletal response to endurance exercise in ovariectomized mice by promoting Akt/β-Catenin Pathway. Front Physiol. 2021 Mar;12:639066. https://doi.org/10.3389/fphys.2021.639066 https://doi.org/10.3389/fphys.2021.63906...
|
|
|
|
Not performed |
r- irisin i.p. (18 ng/ml injections) 2 times/week (3.5 d apart) for 3 weeks. |
2 x 2 factorial ANOVA |
r-irisin did not improve bone mechanical properties |
Intermittent |
Storlino et al., 20203535 Xin X, Wu J, Zheng A, Jiao D, Liu Y, Cao L, et al. Delivery vehicle of muscle-derived irisin based on silk/calcium silicate/sodium alginate composite scaffold for bone regeneration. Int J Nanomedicine. 2019 Feb;14:1451-67. https://doi.org/10.2147/IJN.S193544 https://doi.org/10.2147/IJN.S193544...
|
C57BL6 mice |
Experiment 1: |
Expression of Bcl2 and Bax by qPCR. |
Not performed. |
100 μg/kg r- irisin i.p. injection once a week for four weeks. |
Student t test or ANOVA followed by Tukey’s post hoc analysis. |
r- irisin treatment mitigated apoptotic index by increase of Bcl2/Bax in both hindlimb and old mice bone. |
Intermittent |
|
Control + vehicle group (n = 8). |
Total and cleaved Caspase-9 and Caspase-3 expressions in cortical bone by western blotting. |
r- irisin prevented disuse-induced reduction of viable osteocytes and increase of empty lacunae, as well as Caspase-9 and Caspase-3 activations. |
Male mice |
Hindlimb suspended (HLS) + vehicle group (n = 8). |
Histological analysis of osteocytes survival and empty lacunae of femur cortical bone |
|
|
HLS + r-irisin group (n = 8). |
|
|
Experiment 1: 8 weeks old. |
|
|
|
|
Experiment 2: |
|
|
Experiment 2: 18 months old. |
Old control + vehicle group (n = 8). |
|
|
|
Old + r-irisin group (n = 8). |
|
|
Iemura et al., 20203737 Storlino G, Colaianni G, Sanesi L, Lippo L, Brunetti G, Errede M, et al. Irisin prevents disuse-induced osteocyte apoptosis. J Bone Miner Res. 2020 Apr;35(4):766-75. https://doi.org/10.1002/jbmr.3944 https://doi.org/10.1002/jbmr.3944...
|
C57BL/6J mice |
Experiment 1: |
Quantitative computed tomography (QCT) of tibia. |
Not performed. |
100 μg/kg r- irisin i.p. once a week for eight weeks. |
Mann–Whitney U test or Two-way ANOVA followed by Tukey–Kramer test |
Animals of androgen deficiency groups showed decreased expression of irisin. |
Intermittent |
|
Sham group (n = 8). |
qPCR analysis of Runx2, Osterix, ALP, osteocalcin, type I collagen (Col-1), RANKL and OPG. |
r-irisin treatment significantly blunted trabecular BMD and BV/TV reduction in ORX mice. |
Male (Exp. 1 and 2) |
Orchidectomy (ORX) (n = 8). |
|
BMD and BV/TV in sham-operated animals were similar with or without r-irisin administration. |
20 weeks old |
|
|
|
|
Experiment 2: |
|
|
Iemura et al., 20203737 Storlino G, Colaianni G, Sanesi L, Lippo L, Brunetti G, Errede M, et al. Irisin prevents disuse-induced osteocyte apoptosis. J Bone Miner Res. 2020 Apr;35(4):766-75. https://doi.org/10.1002/jbmr.3944 https://doi.org/10.1002/jbmr.3944...
|
Female (Exp. 3) |
Control/sham group (n = 7). |
|
Not performed. |
100 μg/kg r- irisin i.p. once a week for eight weeks. |
Mann–Whitney U test or Two-way ANOVA followed by Tukey–Kramer test |
|
Intermittent |
7 weeks old |
Control/ORX group (n = 7). |
|
|
|
r-irisin/Sham group (n = 7). |
|
|
|
r-Irisin/ORX group (n = 7). |
|
|
|
Experiment 3 |
|
|
|
Sham surgery (n=8). |
|
|
|
Ovariectomy (OVX) group (n = 8). |
|
|
Xu et al., 20201818 Xu L, Shen L, Yu X, Li P, Wang Q, Li C. Effects of irisin on osteoblast apoptosis and osteoporosis in postmenopausal osteoporosis rats through upregulating Nrf2 and inhibiting NLRP3 inflammasome. Exp Ther Med. 2020 Feb;19(2):1084-90. https://doi.org/10.3892/etm.2019.8313 https://doi.org/10.3892/etm.2019.8313...
|
SPF Sprague-Dawley rats |
Control group (n =15). |
µCT of vertebral bone; osteocalcin, TNF-α, and IL-6 (ELISA assay); serum alkaline phosphatase (ALP) |
Not performed. |
1 mmol/l r-irisin (no information regarding origin, administration via or frequency). |
Not clearly defined. |
ALP significantly increased in OVX group and declined in r-irisin group. |
No information regarding frequency |
|
Ovariectomized (OVX) group (n = 15). |
qPCR for Bcl-2, Caspase-3, Runx2, OC, Nrf2 and NLRP3 |
Levels of TNF-α and IL-6 reduced in OVX animals while OC increased. r-irisin minimized these alterations. |
Female |
OVX + r-irisin group (n = 15). |
|
r-irisin group increased Tb.Th, Tb.N and BMD while Tb.Sp declined compared with that in the OVX group |
|
|
|
r-irisin group increased mRNA expression levels of Runx2, OC, Bcl-2 and Nrf2, while caspase-3 and NLRP3 displayed the opposite trends |
No information regarding age |
|
|
|
He et al., 20204343 He Z, Li H, Han X, Zhou F, Du J, Yang Y, et al. Irisin inhibits osteocyte apoptosis by activating the Erk signaling pathway in vitro and attenuates ALCT-induced osteoarthritis in mice. Bone. 2020 Dec;141:115573. https://doi.org/10.1016/j.bone.2020.115573 https://doi.org/10.1016/j.bone.2020.1155...
|
C57BL/6 mice |
Sham-operated group (n = 10) |
µCT of subchondral bone, trabecular bone below the growth plate, and cortical bone in the tibia. |
Not performed. |
100 μg/kg of r-irisin i.p. weekly for four weeks. |
Unpaired Student t-tests (two-tailed) or one-way ANOVA followed by Newman-Keuls multiple comparison tests. |
Irisin reduced the expression of matrix metalloproteinase (MMP)-13 in cartilage and caspase 3 in the subchondral bone. |
Intermittent |
|
|
|
Bone volume fraction, trabecular number, connection density, and the structure model index was improved by irisin administration. |
He et al., 20204343 He Z, Li H, Han X, Zhou F, Du J, Yang Y, et al. Irisin inhibits osteocyte apoptosis by activating the Erk signaling pathway in vitro and attenuates ALCT-induced osteoarthritis in mice. Bone. 2020 Dec;141:115573. https://doi.org/10.1016/j.bone.2020.115573 https://doi.org/10.1016/j.bone.2020.1155...
|
Male |
Control (Anterior cruciate ligament transection – ACLT- operated) group (n =10) |
Bone histomorphometric analysis |
Not performed. |
100 μg/kg of r-irisin i.p. weekly for four weeks. |
Unpaired Student t-tests (two-tailed) or one-way ANOVA followed by Newman-Keuls multiple comparison tests. |
Irisin increased subchondral bone remodeling, proliferation of osteocytes, and attenuated osteoarthritis progression. |
Intermittent |
3 months old |
ACLT-operated |
|
|
|
+ r-irisin group (n = 10) |
|
|
Luo et al., 20204141 Luo Y, Ma Y, Qiao X, Zeng R, Cheng R, Nie Y, et al. Irisin ameliorates bone loss in ovariectomized mice. Climacteric. 2020 Oct;23(5):496-504. https://doi.org/10.1080/13697137.2020.1745768 https://doi.org/10.1080/13697137.2020.17...
|
C57BL/6 mice |
Sham + saline group (n = 12) |
µCT of cortical and trabecular bone in the femur. |
Not performed. |
100 μg/kg of r-irisin i.p. twice a week for five weeks. |
One-way ANOVA, followed by Tukey’s test. |
Irisin increased bone mineral density, bone volume ratio, connection density, and trabecular parameters. |
Intermittent |
Female |
OVX + saline group (n = 12) |
Strength evaluation of tibia. |
In OVX mice, irisin increased bone stiffness, number of osteoblasts on the trabecular surface and reduction of osteoclasts numbers. |
|
|
|
r-irisin-treated OVX mice presented a higher osteocalcin level and a lower tartrate-resistant acid phosphatase serum concentration. |
10 weeks old |
OVX + r-irisin group (n = 12) |
Bone formation and resorption parameters of distal femurs. |
|
Metzger et al., 20204242 Metzger CE, Anand Narayanan S, Phan PH, Bloomfield SA. Hindlimb unloading causes regional loading-dependent changes in osteocyte inflammatory cytokines that are modulated by exogenous irisin treatment. NPJ Microgravity. 2020 Oct;6(1):28. https://doi.org/10.1038/s41526-020-00118-4 https://doi.org/10.1038/s41526-020-00118...
|
Sprague-Dawley rats |
Control group (n =6) |
Volumetric bone mineral density (accessed by peripheral quantitative computed tomography) of the proximal tibia metaphysis, femoral neck, and proximal humerus. |
Not performed. |
18 ng/ml injections of r-irisin i.p. three times per week for four weeks. |
One-way ANOVA, followed by Tukey HSD post hoc test. |
Irisin treatment increased bone formation rate, and lowered osteoclast surfaces and osteocyte TNF-α, IL-17, RANKL, and sclerostin in the unloaded hindlimb. |
Intermittent |
|
Hindlimb unloaded (HU) group (n = 6) |
|
Male |
|
Dynamic and static cancellous histomorphometry of the proximal tibia metaphysis, femoral neck, fourth lumbar vertebrae, and proximal humerus. |
Metzger et al., 20204242 Metzger CE, Anand Narayanan S, Phan PH, Bloomfield SA. Hindlimb unloading causes regional loading-dependent changes in osteocyte inflammatory cytokines that are modulated by exogenous irisin treatment. NPJ Microgravity. 2020 Oct;6(1):28. https://doi.org/10.1038/s41526-020-00118-4 https://doi.org/10.1038/s41526-020-00118...
|
|
Hindlimb unloaded + r-irisin group (n = 6) |
|
Not performed. |
18 ng/ml injections of r-irisin i.p. three times per week for four weeks. |
One-way ANOVA, followed by Tukey HSD post hoc test. |
Irisin treatment increased bone formation rate, and lowered osteoclast surfaces and osteocyte TNF-α, IL-17, RANKL, and sclerostin in the unloaded hindlimb. |
Intermittent |
8 weeks old |
|
Immunohistochemistry for cathepsin-K-covered bone surfaces. |
Morgan et al., 20214040 Morgan EN, Alsharidah AS, Mousa AM, Edrees HM. Irisin has a protective role against osteoporosis in ovariectomized rats. BioMed Res Int. 2021 Apr;2021:5570229. https://doi.org/10.1155/2021/5570229 https://doi.org/10.1155/2021/5570229...
|
Wistar rats |
Control group (n = 10) |
Calcium content in right femur (detected by an atomic absorption spectrophotometer). |
Not performed. |
100 μg/kg/week of irisin for four weeks (no information regarding via). |
One-way ANOVA, followed by Tukey LSD post hoc test. |
Irisin administration increased dry and ash weight of the femur, as well as concentration of calcium and phosphorus in bone ash. |
Intermittent |
Female |
Sham group (n = 10) |
Inorganic phosphate content (detected by a spectrophotometer according to Plummer’s method). |
OVX + irisin animals presented smooth periosteal and endosteal surfaces with few subperiosteal resorbed bone cavities, numerous osteocytes, and few osteoclasts |
No information regarding age |
OVX + vehicle group (n = 10) |
Number of osteocytes, osteoclasts, and resorbed bone cavities of bone tissue, evaluated by histological examination. |
Irisin treatment reduced serum levels of osteocalcin, bone alkaline phosphatase, tartrate-resistant acid phosphatase, calcium, phosphorus and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). |
|
OVX + irisin group (n = 10) |
|
|
Zhao et al., 20213636 Zhao R, Zhou Y, Li J, Lin J, Cui W, Peng Y, et al. Irisin regulating skeletal response to endurance exercise in ovariectomized mice by promoting Akt/β-Catenin Pathway. Front Physiol. 2021 Mar;12:639066. https://doi.org/10.3389/fphys.2021.639066 https://doi.org/10.3389/fphys.2021.63906...
|
C57BL/6 mice |
Sham group (n = 10) |
µCT of cortical and trabecular bone in the right femur. |
8 weeks of treadmill running protocol, starting with speed gradually increasing (from 8 meters/min to 13 meters/min for 30 minutes in the first week) followed by 5 days/week sections of 45min at a speed of 13 meters/min and with a slope of −9° in the other weeks. |
FNDC5 expression in tibia accessed by Western Blot and RT-PCR techniques. |
One-way ANOVA, followed by Bonferroni post hoc test. |
Exercise promoted mRNA expression of FNDC5 (irisin precursor), Akt and b-catenin, and enhanced serum irisin levels compared to OVX group. |
Continuous |
Zhao et al., 20213636 Zhao R, Zhou Y, Li J, Lin J, Cui W, Peng Y, et al. Irisin regulating skeletal response to endurance exercise in ovariectomized mice by promoting Akt/β-Catenin Pathway. Front Physiol. 2021 Mar;12:639066. https://doi.org/10.3389/fphys.2021.639066 https://doi.org/10.3389/fphys.2021.63906...
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After 3 weeks of surgical operation, Exercise + cyclo RGDyk group mice were treated twice weekly with 2.5 mg/kg cyclo RGDyk. |
FNDC5 expression in tibia accessed by Western Blot and RT-PCR techniques. |
One-way ANOVA, followed by Bonferroni post hoc test. |
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Continuous |
Female |
OVX (n = 10) |
Alkaline phosphatase activity accessed by staining of proximal left tibiae. |
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Exercise increased cortical and trabecular volumetric bone mineral density (vBMD) as well as trabecular bone volume fraction (BV/TV), thickness (Tb.Th), numbers (Tb.N) and separation (Tb.Sp) compared to OVX group. |
3 months old |
OVX + exercise group (n = 10) |
Expression of fibronectin type III domain-containing protein 5 (FNDC5) in right tibia accessed by Western Blot and RT-PCR techniques. |
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Exercise + cyclo RGDyk (anti-irisin receptor agents) group (n = 10) |
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