Running exercise alleviates trabecular bone loss and osteopenia in hemizygous β-globin knockout thalassemic mice.
A marked decrease in β-globin production led to β-thalassemia, a hereditary anemic disease associated with bone marrow expansion, bone erosion, and osteoporosis. Herein, we aimed to investigate changes in bone mineral density (BMD) and trabecular microstructure in hemizygous β-globin knockout thalassemic (BKO) mice and to determine whether endurance running (60 min/day, 5 days/wk for 12 wk in running wheels) could effectively alleviate bone loss in BKO mice. Both male and female BKO mice (1-2 mo old) showed growth retardation as indicated by smaller body weight and femoral length than their wild-type littermates. A decrease in BMD was more severe in female than in male BKO mice. Bone histomorphometry revealed that BKO mice had decreases in trabecular bone volume, trabecular number, and trabecular thickness, presumably due to suppression of osteoblast-mediated bone formation and activation of osteoclast-mediated bone resorption, the latter of which was consistent with elevated serum levels of osteoclastogenic cytokines IL-1α and -1β. As determined by peripheral quantitative computed tomography, running increased cortical density and thickness in the femoral and tibial diaphyses of BKO mice compared with those of sedentary BKO mice. Several histomorphometric parameters suggested an enhancement of bone formation (e.g., increased mineral apposition rate) and suppression of bone resorption (e.g., decreased osteoclast surface), which led to increases in trabecular bone volume and trabecular thickness in running BKO mice. In conclusion, BKO mice exhibited pervasive osteopenia and impaired bone microstructure, whereas running exercise appeared to be an effective intervention in alleviating bone microstructural defect in β-thalassemia.
Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok, Thailand; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand; Exercise Science Graduate Program, Faculty of Science, Mahidol University, Bangkok, Thailand; and.
Kanogwun
K
Thongchote
Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.
Saovaros
S
Svasti
Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok, Thailand; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand;
Jarinthorn
J
Teerapornpuntakit
Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok, Thailand; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand;
Nateetip
N
Krishnamra
Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok, Thailand; Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand; naratt@narattsys.com.
Narattaphol
N
Charoenphandhu
D015502:Absorptiometry, Photon; D000375:Aging; D000818:Animals; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000000981:diagnostic imaging / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D001862:Bone Resorption / Q000000981:diagnostic imaging / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D001842:Bone and Bones / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology; D005260:Female; D057898:Hemizygote; D053582:Interleukin-1alpha / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D005082:Physical Exertion; D011897:Random Allocation; D012727:Sex Characteristics; D013789:Thalassemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D015854:Up-Regulation; D055544:beta-Globins / Q000235:genetics / Q000378:metabolism*
C587672:IL1B protein, mouse; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D055544:beta-Globins
bone histomorphometry; bone mineral density; endurance exercise; osteoporosis; running wheel