Osteoblast/osteocyte-derived interleukin-11 regulates osteogenesis and systemic adipogenesis

被引：46

作者：

Dong, Bingzi ^{[1
,2
,3
]}

Hiasa, Masahiro ^{[4
]}

Higa, Yoshiki ^{[4
]}

Ohnishi, Yukiyo ^{[2
]}

Endo, Itsuro ^{[2
]}

Kondo, Takeshi ^{[2
]}

Takashi, Yuichi ^{[1
]}

Tsoumpra, Maria ^{[1
]}

Kainuma, Risa ^{[1
,5
]}

Sawatsubashi, Shun ^{[1
]}

Kiyonari, Hiroshi ^{[6
]}

Shioi, Go ^{[6
]}

Sakaue, Hiroshi ^{[7
]}

Nakashima, Tomoki ^{[8
]}

Kato, Shigeaki ^{[9
]}

Abe, Masahiro ^{[2
]}

Fukumoto, Seiji ^{[1
]}

Matsumoto, Toshio ^{[1
]}

机构：

[1] Tokushima Univ, Fujii Mem Inst Med Sci, Tokushima, Japan

[2] Tokushima Univ, Dept Endocrinol Metab & Hematol, Grad Sch Med Sci, Tokushima, Japan

[3] Qingdao Univ, Dept Endocrinol & Metab, Affiliated Hosp, Qingdao, Peoples R China

[4] Tokushima Univ, Dept Orthodont & Dentofacial Orthoped, Grad Sch Dent, Tokushima, Japan

[5] Setsuro Tech Inc, Tokushima, Japan

[6] RIKEN Ctr Biosyst Dynam Res, Lab Anim Resources & Genet Engn, Kobe, Hyogo, Japan

[7] Tokushima Univ, Dept Nutr & Metab, Grad Sch Nutr Sci, Tokushima, Japan

[8] Tokyo Med & Dent Univ, Dept Cell Signaling, Tokyo, Japan

[9] Fukushima Med Univ, Fukushima, Japan

来源：

NATURE COMMUNICATIONS | 2022年 / 13卷 / 01期

基金：

日本学术振兴会;

关键词：

BONE-FORMATION; EXPRESSION; GENE; DIFFERENTIATION; OSTEOBLASTS; IL-11; LINE;

D O I：

10.1038/s41467-022-34869-3

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：

Here, the authors identify interleukin-11 as a mediator of bone-adipose crosstalk during mechanical loading of the bone. Interleukin-11 secreted by the bone acts as a hormone to regulate fat metabolism, in addition to having an autocrine-paracrine effect on bone itself. Exercise results in mechanical loading of the bone and stimulates energy expenditure in the adipose tissue. It is therefore likely that the bone secretes factors to communicate with adipose tissue in response to mechanical loading. Interleukin (IL)-11 is known to be expressed in the bone, it is upregulated by mechanical loading, enhances osteogenesis and suppresses adipogenesis. Here, we show that systemic IL-11 deletion (IL-11(-/-)) results in reduced bone mass, suppressed bone formation response to mechanical loading, enhanced expression of Wnt inhibitors, and suppressed Wnt signaling. At the same time, the enhancement of bone resorption by mechanical unloading was unaffected. Unexpectedly, IL-11(-/-) mice have increased systemic adiposity and glucose intolerance. Osteoblast/osteocyte-specific IL-11 deletion in osteocalcin-Cre;IL-11(fl/fl) mice have reduced serum IL-11 levels, blunted bone formation under mechanical loading, and increased systemic adiposity similar to IL-11(-/-) mice. Adipocyte-specific IL-11 deletion in adiponectin-Cre;IL-11(fl/fl) did not exhibit any abnormalities. We demonstrate that osteoblast/osteocyte-derived IL-11 controls both osteogenesis and systemic adiposity in response to mechanical loading, an important insight for our understanding of osteoporosis and metabolic syndromes.

引用

页数：17

共 37 条

[31] Activation of unliganded FGF receptor by extracellular phosphate potentiates proteolytic protection of FGF23 by its O-glycosylation [J].