PMID- 28589412 OWN - NLM STAT- MEDLINE DCOM- 20180618 LR - 20181202 IS - 1435-5604 (Electronic) IS - 0914-8779 (Linking) VI - 36 IP - 3 DP - 2018 May TI - Serum CTX levels and histomorphometric analysis in Src versus RANKL knockout mice. PG - 264-273 LID - 10.1007/s00774-017-0838-3 [doi] AB - 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. FAU - Takeshita, Sunao AU - Takeshita S AD - Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi, 474-8511, Japan. sunao@ncgg.go.jp. FAU - Fumoto, Toshio AU - Fumoto T AD - Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi, 474-8511, Japan. FAU - Ito, Masako AU - Ito M AD - Medical Work-Life-Balance Center, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. FAU - Ikeda, Kyoji AU - Ikeda K AD - Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi, 474-8511, Japan. LA - eng GR - 22390064/Japan Society for the Promotion of Science (JP)/ GR - 21790374/JSPS/ GR - 22118007/MEXT/ GR - H23-12/Ministry of Health, Labour and Welfare/ GR - H26-17/Ministry of Health, Labour and Welfare/ PT - Comparative Study PT - Journal Article DEP - 20170606 PL - Japan TA - J Bone Miner Metab JT - Journal of bone and mineral metabolism JID - 9436705 RN - 0 (Biomarkers) RN - 0 (Collagen Type I) RN - 0 (Peptides) RN - 0 (RANK Ligand) RN - 0 (collagen type I trimeric cross-linked peptide) RN - 104982-03-8 (Osteocalcin) RN - EC 2.7.10.2 (src-Family Kinases) RN - EC 3.1.3.2 (Tartrate-Resistant Acid Phosphatase) SB - IM MH - Animals MH - Biomarkers/metabolism MH - Bone Resorption/blood/genetics/metabolism MH - Collagen Type I/*blood MH - Gene Expression Regulation MH - Imaging, Three-Dimensional MH - Mice MH - Mice, Knockout MH - Osteoblasts/metabolism MH - Osteocalcin/blood MH - Osteoclasts/metabolism MH - Osteocytes/metabolism MH - Peptides/*blood MH - RANK Ligand/*deficiency MH - Tartrate-Resistant Acid Phosphatase/blood MH - Tibia/diagnostic imaging/pathology MH - X-Ray Microtomography MH - src-Family Kinases/*deficiency OTO - NOTNLM OT - Osteoblast OT - Osteoclast OT - Osteocyte OT - Osteopetrosis EDAT- 2017/06/08 06:00 MHDA- 2018/06/19 06:00 CRDT- 2017/06/08 06:00 PHST- 2016/03/29 00:00 [received] PHST- 2017/03/28 00:00 [accepted] PHST- 2017/06/08 06:00 [pubmed] PHST- 2018/06/19 06:00 [medline] PHST- 2017/06/08 06:00 [entrez] AID - 10.1007/s00774-017-0838-3 [pii] AID - 10.1007/s00774-017-0838-3 [doi] PST - ppublish SO - J Bone Miner Metab. 2018 May;36(3):264-273. doi: 10.1007/s00774-017-0838-3. Epub 2017 Jun 6.