Browsing by Author "Rosen, Clifford J."

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    Deletion of FNDC5/Irisin modifies murine osteocyte function in a sex-specific manner
    (bioRxiv, 2024-03-20) Shimonty, Anika; Pin, Fabrizio; Prideaux, Matt; Peng, Gang; Huot, Joshua R.; Kim, Hyeonwoo; Rosen, Clifford J.; Spiegelman, Bruce M.; Bonewald, Lynda F.; Anatomy, Cell Biology and Physiology, School of Medicine
    Irisin, released from exercised muscle, has been shown to have beneficial effects on numerous tissues but its effects on bone are unclear. We found significant sex and genotype differences in bone from wildtype (WT) mice compared to mice lacking Fndc5 (KO), with and without calcium deficiency. Despite their bone being indistinguishable from WT females, KO female mice were partially protected from osteocytic osteolysis and osteoclastic bone resorption when allowed to lactate or when placed on a low-calcium diet. Male KO mice have more but weaker bone compared to WT males, and when challenged with a low-calcium diet lost more bone than WT males. To begin to understand responsible molecular mechanisms, osteocyte transcriptomics was performed. Osteocytes from WT females had greater expression of genes associated with osteocytic osteolysis and osteoclastic bone resorption compared to WT males which had greater expression of genes associated with steroid and fatty acid metabolism. Few differences were observed between female KO and WT osteocytes, but with a low calcium diet, the KO females had lower expression of genes responsible for osteocytic osteolysis and osteoclastic resorption than the WT females. Male KO osteocytes had lower expression of genes associated with steroid and fatty acid metabolism, but higher expression of genes associated with bone resorption compared to male WT. In conclusion, irisin plays a critical role in the development of the male but not the female skeleton and protects male but not female bone from calcium deficiency. We propose irisin ensures the survival of offspring by targeting the osteocyte to provide calcium in lactating females, a novel function for this myokine.
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    Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors
    (Elsevier, 2018-12-13) Kim, Hyeonwoo; Wrann, Christiane D.; Jedrychowski, Mark; Vidoni, Sara; Kitase, Yukiko; Nagano, Kenichi; Zhou, Chenhe; Chou, Joshua; Parkman, Virginia-Jeni A.; Novick, Scott J.; Strutzenberg, Timothy S.; Pascal, Bruce D.; Le, Phuong T.; Brooks, Daniel J.; Roche, Alexander M.; Gerber, Kaitlyn K.; Mattheis, Laura; Chen, Wenjing; Tu, Hua; Bouxsein, Mary L.; Griffin, Patrick R.; Baron, Roland; Rosen, Clifford J.; Bonewald, Lynda F.; Spiegelman, Bruce M.; Orthopaedic Surgery, School of Medicine
    Irisin is secreted by muscle, increases with exercise, and mediates certain favorable effects of physical activity. In particular, irisin has been shown to have beneficial effects in adipose tissues, brain, and bone. However, the skeletal response to exercise is less clear, and the receptor for irisin has not been identified. Here we show that irisin binds to proteins of the αV class of integrins, and biophysical studies identify interacting surfaces between irisin and αV/β5 integrin. Chemical inhibition of the αV integrins blocks signaling and function by irisin in osteocytes and fat cells. Irisin increases both osteocytic survival and production of sclerostin, a local modulator of bone remodeling. Genetic ablation of FNDC5 (or irisin) completely blocks osteocytic osteolysis induced by ovariectomy, preventing bone loss and supporting an important role of irisin in skeletal remodeling. Identification of the irisin receptor should greatly facilitate our understanding of irisin's function in exercise and human health.
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    Response to correspondence on “Reproducibility of CRISPR-Cas9 methods for generation of conditional mouse alleles: a multi-center evaluation”
    (BMC, 2021-04-07) Gurumurthy, Channabasavaiah B.; O’Brien, Aidan R.; Quadros, Rolen M.; Adams, John, Jr.; Alcaide, Pilar; Ayabe, Shinya; Ballard, Johnathan; Batra, Surinder K.; Beauchamp, Marie-Claude; Becker, Kathleen A.; Bernas, Guillaume; Brough, David; Carrillo-Salinas, Francisco; Chan, Wesley; Chen, Hanying; Dawson, Ruby; DeMambro, Victoria; D’Hont, Jinke; Dibb, Katharine; Eudy, James D.; Gan, Lin; Gao, Jing; Gonzales, Amy; Guntur, Anyonya; Guo, Huiping; Harms, Donald W.; Harrington, Anne; Hentges, Kathryn E.; Humphreys, Neil; Imai, Shiho; Ishii, Hideshi; Iwama, Mizuho; Jonasch, Eric; Karolak, Michelle; Keavney, Bernard; Khin, Nay-Chi; Konno, Masamitsu; Kotani, Yuko; Kunihiro, Yayoi; Lakshmanan, Imayavaramban; Larochelle, Catherine; Lawrence, Catherine B.; Li, Lin; Lindner, Volkhard; Liu, Xian-De; Lopez-Castejon, Gloria; Loudon, Andrew; Lowe, Jenna; Jerome-Majeweska, Loydie; Matsusaka, Taiji; Miura, Hiromi; Miyasaka, Yoshiki; Morpurgo, Benjamin; Moty, Katherine; Nabeshima, Yo-ichi; Nakade, Koji; Nakashiba, Toshiaki; Nakashima, Kenichi; Obata, Yuichi; Ogiwara, Sanae; Ouellet, Mariette; Oxburgh, Leif; Piltz, Sandra; Pinz, Ilka; Ponnusamy, Moorthy P.; Ray, David; Redder, Ronald J.; Rosen, Clifford J.; Ross, Nikki; Ruhe, Mark T.; Ryzhova, Larisa; Salvador, Ane M.; Shameen Alam, Sabrina; Sedlacek, Radislav; Sharma, Karan; Smith, Chad; Staes, Katrien; Starrs, Lora; Sugiyama, Fumihiro; Takahashi, Satoru; Tanaka, Tomohiro; Trafford, Andrew; Uno, Yoshihiro; Vanhoutte, Leen; Vanrockeghem, Frederique; Willis, Brandon J.; Wright, Christian S.; Yamauchi, Yuko; Yi, Xin; Yoshimi, Kazuto; Zhang, Xuesong; Zhang, Yu; Ohtsuka, Masato; Das, Satyabrata; Garry, Daniel J.; Hochepied, Tino; Thomas, Paul; Parker-Thornburg, Jan; Adamson, Antony D.; Yoshiki, Atsushi; Schmouth, Jean-Francois; Golovko, Andrei; Thompson, William R.; Lloyd, K.C. Kent; Wood, Joshua A.; Cowan, Mitra; Mashimo, Tomoji; Mizuno, Seiya; Zhu, Hao; Kasparek, Petr; Liaw, Lucy; Miano, Joseph M.; Burgio, Gaetan; Medicine, School of Medicine