Mice Lacking the Calcitonin Receptor Do Not Display Improved Bone Healing
Jessika Appelt,
Serafeim Tsitsilonis,
Ellen Otto,
Denise Jahn,
Paul Köhli,
Anke Baranowsky,
Shan Jiang,
Melanie Fuchs,
Christian H. Bucher,
Georg N. Duda,
Karl-Heinz Frosch,
Johannes Keller
Affiliations
Jessika Appelt
Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Hum-boldt-Universität zu Berlin, Center for Musculoskeletal Surgery (CMSC), Augustenburger Platz 1, 13353 Berlin, Germany
Serafeim Tsitsilonis
Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Hum-boldt-Universität zu Berlin, Center for Musculoskeletal Surgery (CMSC), Augustenburger Platz 1, 13353 Berlin, Germany
Ellen Otto
Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Hum-boldt-Universität zu Berlin, Center for Musculoskeletal Surgery (CMSC), Augustenburger Platz 1, 13353 Berlin, Germany
Denise Jahn
Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Hum-boldt-Universität zu Berlin, Center for Musculoskeletal Surgery (CMSC), Augustenburger Platz 1, 13353 Berlin, Germany
Paul Köhli
Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Hum-boldt-Universität zu Berlin, Center for Musculoskeletal Surgery (CMSC), Augustenburger Platz 1, 13353 Berlin, Germany
Anke Baranowsky
Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Shan Jiang
Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Melanie Fuchs
Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Hum-boldt-Universität zu Berlin, Center for Musculoskeletal Surgery (CMSC), Augustenburger Platz 1, 13353 Berlin, Germany
Christian H. Bucher
Berlin Institute of Health at Charité–Universitätsmedizin Berlin, Julius Wolff Institute (JWI), Au-gustenburger Platz 1, 13353 Berlin, Germany
Georg N. Duda
Berlin Institute of Health at Charité–Universitätsmedizin Berlin, Julius Wolff Institute (JWI), Au-gustenburger Platz 1, 13353 Berlin, Germany
Karl-Heinz Frosch
Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Johannes Keller
Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Despite significant advances in surgical techniques, treatment options for impaired bone healing are still limited. Inadequate bone regeneration is not only associated with pain, prolonged immobilization and often multiple revision surgeries, but also with high socioeconomic costs, underlining the importance of a detailed understanding of the bone healing process. In this regard, we previously showed that mice lacking the calcitonin receptor (CTR) display increased bone formation mediated through the increased osteoclastic secretion of sphingosine-1-phosphate (S1P), an osteoanabolic molecule promoting osteoblast function. Although strong evidence is now available for the crucial role of osteoclast-to-osteoblast coupling in normal bone hemostasis, the relevance of this paracrine crosstalk during bone regeneration is unknown. Therefore, our study was designed to test whether increased osteoclast-to-osteoblast coupling, as observed in CTR-deficient mice, may positively affect bone repair. In a standardized femoral osteotomy model, global CTR-deficient mice displayed no alteration in radiologic callus parameters. Likewise, static histomorphometry demonstrated moderate impairment of callus microstructure and normal osseous bridging of osteotomy ends. In conclusion, bone regeneration is not accelerated in CTR-deficient mice, and contrary to its osteoanabolic action in normal bone turnover, osteoclast-to-osteoblast coupling specifically involving the CTR-S1P axis, may only be of minor relevance during bone healing.
