The myokine irisin increases cortical bone mass

被引:399
作者
Colaianni, Graziana [1 ]
Cuscito, Concetta [1 ]
Mongelli, Teresa [1 ]
Pignataro, Paolo [1 ]
Buccoliero, Cinzia [1 ]
Liu, Peng [2 ,3 ]
Lu, Ping [2 ,3 ]
Sartini, Loris [4 ]
Di Comite, Mariasevera [1 ]
Mori, Giorgio [5 ]
Di Benedetto, Adriana [5 ]
Brunetti, Giacomina [1 ]
Yuen, Tony [2 ,3 ]
Sun, Li [2 ,3 ]
Reseland, Janne E. [6 ]
Colucci, Silvia [1 ]
New, Maria I. [2 ,3 ]
Zaidi, Mone [2 ,3 ]
Cinti, Saverio [4 ]
Grano, Maria [1 ]
机构
[1] Univ Bari, Dept Basic Med Sci Neurosci & Sense Organs, I-70124 Bari, Italy
[2] Mt Sinai Sch Med, Dept Med, Mt Sinai Bone Program, New York, NY 10029 USA
[3] Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA
[4] Univ Ancona, Ctr Obes, United Hosp, Dept Expt & Clin Med, I-60020 Ancona, Italy
[5] Univ Foggia, Dept Clin & Expt Med, I-71100 Foggia, Italy
[6] Univ Oslo, Inst Clin Dent, Dept Biomat, N-0317 Oslo, Norway
基金
美国国家卫生研究院;
关键词
mechanical loading; sarcopenia; osteoporosis; BROWN ADIPOSE-TISSUE; MINERAL DENSITY; OSTEOPOROTIC FRACTURES; CLIMBING EXERCISE; BODY-COMPOSITION; WHITE FAT; STRENGTH; ADIPOCYTES; GROWTH; CELLS;
D O I
10.1073/pnas.1516622112
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 mu g 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 mu g 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 Ppar gamma expression in white adipose tissue. In bone marrow stromal cell cultures, r-irisin rapidly phosphorylated Erk, and up-regulated Atf4, Runx2, Osx, Lrp5, beta-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.
引用
收藏
页码:12157 / 12162
页数:6
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