Parathyroid Hormone Inhibits Fatty Infiltration and Muscle Atrophy After Rotator Cuff Tear by Browning of Fibro-adipogenic Progenitors in a Rodent Model

被引:9
作者
Iio, Ryosuke [1 ,2 ,3 ]
Manaka, Tomoya [1 ,2 ]
Takada, Naoki [1 ,2 ]
Orita, Kumi [1 ,2 ]
Nakazawa, Katsumasa [1 ,2 ,3 ]
Hirakawa, Yoshihiro [1 ,2 ]
Ito, Yoichi [1 ,4 ]
Nakamura, Hiroaki [1 ,2 ]
机构
[1] Osaka City Univ, Grad Sch Med, Osaka, Japan
[2] Osaka Metropolitan Univ, Dept Orthopaed Surg, Grad Sch Med, 1-4-3 Asahi Machi,Abeno Ku, Osaka 5458585, Japan
[3] Osaka City Univ, Dept Orthopaed Surg, Grad Sch Med, Osaka, Japan
[4] Osaka Shoulder Ctr, Ito Clin, Osaka, Japan
关键词
rotator cuff tears; fibro-adipogenic progenitors; parathyroid hormone; fatty infiltration; muscle atrophy; ENDOTHELIAL GROWTH-FACTOR; DISTINCT; REPAIR; MOUSE; CELLS; UCP1;
D O I
10.1177/03635465231190389
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
Background: Progressive fatty infiltration and muscle atrophy after rotator cuff tears lead to tendon repair failure and poor outcomes. Fibro-adipogenic progenitors (FAPs) are involved in fatty infiltration and muscle homeostasis of skeletal muscle. Inducing FAP differentiation into brown adipocyte-like ''beige adipocytes'' suppresses fatty infiltration and muscle atrophy. Hypothesis: Parathyroid hormone (PTH) suppresses fatty infiltration and muscle atrophy after rotator cuff tears in a rat model by browning of FAPs. Study Design: Controlled laboratory study. Methods: PTH was administered subcutaneously for 4 or 8 weeks to a rotator cuff tear model in rats. After treatment, fatty infiltration of supraspinatus muscles was assessed using Oil Red O staining and muscle atrophy using wet muscle weight and muscle fiber cross-sectional area. Costaining of platelet-derived growth factor receptor a (FAP marker) and uncoupling protein 1 (browning marker) was performed to confirm FAP browning by PTH. Mouse-isolated FAPs were cultured with PTH and evaluated for browning-related gene expression and adipogenic differentiation using BODIPY staining. Myogenic differentiation of C2C12 myoblasts was evaluated using coculture of PTH-treated browning FAPs with C2C12. Results: PTH inhibited fatty infiltration after rotator cuff tear at 8 weeks. Rotator cuff wet muscle loss of PTH-treated rats was inhibited at 4 and 8 weeks. Furthermore, PTH-treated rats demonstrated larger myofiber cross-sectional area than did untreated rats at 4 and 8 weeks. Costaining indicated colocalization of platelet-derived growth factor receptor a and uncoupling protein 1 and promoted PTH-induced FAP browning. PTH increased the expression of browning-related genes in FAPs and suppressed fat droplet accumulation in vitro. Coculture with PTH-treated FAPs promoted C2C12 cell differentiation into myotubes. Conclusion: PTH induced FAP-derived beige adipocytes by upregulating browning-related gene expression, and the browning effect of PTH on FAPs inhibited fatty infiltration and muscle atrophy in the rat rotator cuff tear model. PTH might have potential as a therapeutic drug for fatty infiltration and muscle atrophy after rotator cuff tears. Clinical Relevance: PTH may expand treatment options for rotator cuff tears by reducing fatty infiltration and muscle atrophy after rotator cuff tears by browning of FAPs.
引用
收藏
页码:3251 / 3260
页数:10
相关论文
共 33 条
[11]   Regulatory circuits controlling white versus brown adipocyte differentiation [J].
Hansen, Jacob B. ;
Kristiansen, Karsten .
BIOCHEMICAL JOURNAL, 2006, 398 :153-168
[12]   Brown and beige fat: development, function and therapeutic potential [J].
Harms, Matthew ;
Seale, Patrick .
NATURE MEDICINE, 2013, 19 (10) :1252-1263
[13]   Parathyroid hormone induces a browning program in human white adipocytes [J].
Hedesan, Oana C. ;
Fenzl, Anna ;
Digruber, Astrid ;
Spirk, Katrin ;
Baumgartner-Parzer, Sabina ;
Bilban, Martin ;
Kenner, Lukas ;
Vierhapper, Martin ;
Elbe-Burger, Adelheid ;
Kiefer, Florian W. .
INTERNATIONAL JOURNAL OF OBESITY, 2019, 43 (06) :1319-1324
[14]   Fibroadipogenic progenitors are responsible for muscle loss in limb girdle muscular dystrophy 2B [J].
Hogarth, Marshall W. ;
Defour, Aurelia ;
Lazarski, Christopher ;
Gallardo, Eduard ;
Diaz Manera, Jordi ;
Partridge, Terence A. ;
Nagaraju, Kanneboyina ;
Jaiswal, Jyoti K. .
NATURE COMMUNICATIONS, 2019, 10 (1)
[15]   Factors Predictive of Healing in Large Rotator Cuff Tears Is It Possible to Predict Retear Preoperatively? [J].
Jeong, Ho Yeon ;
Kim, Hwan Jin ;
Jeon, Yoon Sang ;
Rhee, Yong Girl .
AMERICAN JOURNAL OF SPORTS MEDICINE, 2018, 46 (07) :1693-1700
[16]   Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis [J].
Joe, Aaron W. B. ;
Yi, Lin ;
Natarajan, Anuradha ;
Le Grand, Fabien ;
So, Leslie ;
Wang, Joy ;
Rudnicki, Michael A. ;
Rossi, Fabio M. V. .
NATURE CELL BIOLOGY, 2010, 12 (02) :153-U144
[17]   Beige fibro-adipogenic progenitor transplantation reduces muscle degeneration and improves function in a mouse model of delayed repair of rotator cuff tears [J].
Lee, Carlin ;
Liu, Mengyao ;
Agha, Obiajulu ;
Kim, Hubert T. ;
Liu, Xuhui ;
Feeley, Brian T. .
JOURNAL OF SHOULDER AND ELBOW SURGERY, 2020, 29 (04) :719-727
[18]   Autocrine effect of vascular endothelial growth factor-A is essential for mitochondrial function in brown adipocytes [J].
Mandaviani, Kiana ;
Chess, David ;
Wu, Yuanyuan ;
Shirihai, Orian ;
Aprahamian, Tamar R. .
METABOLISM-CLINICAL AND EXPERIMENTAL, 2016, 65 (01) :26-35
[19]   PGC-1α is induced by parathyroid hormone and coactivates Nurr1-mediated promoter activity in osteoblasts [J].
Nervina, Jeanne M. ;
Magyar, Clara E. ;
Pirih, Flavia Q. ;
Tetradis, Sotirios .
BONE, 2006, 39 (05) :1018-1025
[20]   Role of fibro-adipogenic progenitor cells in muscle atrophy and musculoskeletal diseases [J].
Parker, Emily ;
Hamrick, W. Mark .
CURRENT OPINION IN PHARMACOLOGY, 2021, 58 :1-7