Abstract
Src knockout (KO) and RANKL KO mice both exhibit near complete osteopetrosis in terms of 3D-bone volume (BV) fraction by micro-CT, whereas the serum CTX concentration of Src KO is apparently normal and that of RANKL KO is 30% of wild-type (WT) despite the fact that they lack osteoclasts. By histomorphometry we found that, whereas eroded surface (ES) and osteoid surface (OS) are zero values in RANKL KO, they are indistinguishable from WT in Src KO; because of marked increase in bone surface (BS), ES/BS and OS/BS of Src KO are 30–40% of WT. While RANKL KO lack both osteoclasts and osteoblasts, Src KO reveal increased numbers of osteoclasts and indistinguishable numbers of osteoblasts compared with WT; again, on the basis of BS, N.Oc/BS is comparable to WT and N.Ob/BS is markedly decreased in Src KO. The apparently increased number of total osteoclasts may be due to increased expression of RANKL found in Src KO bone in vivo. Src has a gene dosage-dependent effect on osteoclast function in vitro, with Src−/− osteoclasts completely lacking bone-resorbing function as determined by CTX release on dentin. Thus, Src KO osteoclasts retain some bone-resorbing function in vivo. The number of osteocytes is proportionally increased in RANKL KO, while Src KO mice have relative osteocyte deficiency, raising the possibility that RANKL and Src has an unrecognized role in osteocyte survival.
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Acknowledgements
We thank M. Okabe for permission to use CAG-Cre mice, and M. Suzuki for technical assistance. This study was supported by JSPS KAKENHI for Scientific Research B (22390064 to K.I.) and for Young Investigator (21790374 to T.F.) and by MEXT KAKENHI for Scientific Research on Innovative Areas (22118007 to K.I.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; and by a Grant for Longevity Sciences from the Ministry of Health, Labor, and Welfare of Japan (H23-12 to K.I., S.T. and M.I. and H26-17 to S.T., K.I. and M.I.).
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Takeshita, S., Fumoto, T., Ito, M. et al. Serum CTX levels and histomorphometric analysis in Src versus RANKL knockout mice. J Bone Miner Metab 36, 264–273 (2018). https://doi.org/10.1007/s00774-017-0838-3
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DOI: https://doi.org/10.1007/s00774-017-0838-3