title: A Role for the Calcitonin Receptor to Limit Bone Loss During Lactation in Female Mice by Inhibiting Osteocytic Osteolysis.
abstract: During lactation, the large transfer of calcium from the mother to the milk is primarily sourced from the maternal skeleton. To determine whether the calcitonin receptor (CTR) plays a physiological role to protect the skeleton from excessive resorption during lactation, we assessed the maternal skeleton of global CTR knockout (CTRKO) and littermate control mice at the end of lactation (postnatal day 21). Micro-computed tomography analyses showed no effect on trabecular or cortical bone in the distal femur and L1 vertebra of maternal global CTR deletion at the end of lactation in global CTRKO mice compared with that in control mice. Bone resorption, as assessed by osteoclast number and activity at the end of lactation, was unaffected by maternal CTR deletion. Cathepsin K, carbonic anhydrase 2, matrix metalloproteinase 13, and receptor activator of nuclear factor-κB ligand mRNA levels, however, were markedly elevated by 3- to 6.5-fold in whole bone of lactating global CTRKO females. Because these genes have been shown to be up-regulated in osteocytes during lactation when osteocytes resorb their surrounding bone matrix, together with their reported expression of the CTR, we determined the osteocyte lacunar area in cortical bone. After lactation, the top 20% of osteocyte lacunar area in global CTRKO mice was 10% larger than the top 20% in control mice. These data are consistent with an increased osteocytic osteolysis in global CTRKO mice during lactation, which is further supported by the increased serum calcium observed in global CTRKO mice after lactation. These results provide evidence for a physiological role for the CTR to protect the maternal skeleton during lactation by a direct action on osteocytes to inhibit osteolysis.
authors.affiliation: Department of Medicine (M.V.C., P.K.R., S.S., J.P.S., J.D.Z., R.A.D.), Austin Health, University of Melbourne, Heidelberg, 3084 Victoria, Australia; Centre for Orthopaedic and Trauma Research (D.M.F., G.J.A.), University of Adelaide, 5005 Adelaide, Australia; and School of Pharmacy and Medical Sciences (P.H.A.), University of South Australia, 5005 Adelaide, Australia.
authors.forename: Michele V
authors.initials: MV
authors.lastname: Clarke
authors.affiliation: Department of Medicine (M.V.C., P.K.R., S.S., J.P.S., J.D.Z., R.A.D.), Austin Health, University of Melbourne, Heidelberg, 3084 Victoria, Australia; Centre for Orthopaedic and Trauma Research (D.M.F., G.J.A.), University of Adelaide, 5005 Adelaide, Australia; and School of Pharmacy and Medical Sciences (P.H.A.), University of South Australia, 5005 Adelaide, Australia.
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Russell
authors.affiliation: Department of Medicine (M.V.C., P.K.R., S.S., J.P.S., J.D.Z., R.A.D.), Austin Health, University of Melbourne, Heidelberg, 3084 Victoria, Australia; Centre for Orthopaedic and Trauma Research (D.M.F., G.J.A.), University of Adelaide, 5005 Adelaide, Australia; and School of Pharmacy and Medical Sciences (P.H.A.), University of South Australia, 5005 Adelaide, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Findlay
authors.affiliation: Department of Medicine (M.V.C., P.K.R., S.S., J.P.S., J.D.Z., R.A.D.), Austin Health, University of Melbourne, Heidelberg, 3084 Victoria, Australia; Centre for Orthopaedic and Trauma Research (D.M.F., G.J.A.), University of Adelaide, 5005 Adelaide, Australia; and School of Pharmacy and Medical Sciences (P.H.A.), University of South Australia, 5005 Adelaide, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Sastra
authors.affiliation: Department of Medicine (M.V.C., P.K.R., S.S., J.P.S., J.D.Z., R.A.D.), Austin Health, University of Melbourne, Heidelberg, 3084 Victoria, Australia; Centre for Orthopaedic and Trauma Research (D.M.F., G.J.A.), University of Adelaide, 5005 Adelaide, Australia; and School of Pharmacy and Medical Sciences (P.H.A.), University of South Australia, 5005 Adelaide, Australia.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Anderson
authors.affiliation: Department of Medicine (M.V.C., P.K.R., S.S., J.P.S., J.D.Z., R.A.D.), Austin Health, University of Melbourne, Heidelberg, 3084 Victoria, Australia; Centre for Orthopaedic and Trauma Research (D.M.F., G.J.A.), University of Adelaide, 5005 Adelaide, Australia; and School of Pharmacy and Medical Sciences (P.H.A.), University of South Australia, 5005 Adelaide, Australia.
authors.forename: Jarrod P
authors.initials: JP
authors.lastname: Skinner
authors.affiliation: Department of Medicine (M.V.C., P.K.R., S.S., J.P.S., J.D.Z., R.A.D.), Austin Health, University of Melbourne, Heidelberg, 3084 Victoria, Australia; Centre for Orthopaedic and Trauma Research (D.M.F., G.J.A.), University of Adelaide, 5005 Adelaide, Australia; and School of Pharmacy and Medical Sciences (P.H.A.), University of South Australia, 5005 Adelaide, Australia.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Atkins
authors.affiliation: Department of Medicine (M.V.C., P.K.R., S.S., J.P.S., J.D.Z., R.A.D.), Austin Health, University of Melbourne, Heidelberg, 3084 Victoria, Australia; Centre for Orthopaedic and Trauma Research (D.M.F., G.J.A.), University of Adelaide, 5005 Adelaide, Australia; and School of Pharmacy and Medical Sciences (P.H.A.), University of South Australia, 5005 Adelaide, Australia.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Zajac
authors.affiliation: Department of Medicine (M.V.C., P.K.R., S.S., J.P.S., J.D.Z., R.A.D.), Austin Health, University of Melbourne, Heidelberg, 3084 Victoria, Australia; Centre for Orthopaedic and Trauma Research (D.M.F., G.J.A.), University of Adelaide, 5005 Adelaide, Australia; and School of Pharmacy and Medical Sciences (P.H.A.), University of South Australia, 5005 Adelaide, Australia.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Davey
mesh_terms: D000818:Animals; D001846:Bone Development; D002118:Calcium / Q000097:blood; D005260:Female; D007774:Lactation / Q000378:metabolism*; D018345:Mice, Knockout; D010011:Osteocytes / Q000502:physiology*; D010014:Osteolysis; D011247:Pregnancy; D018003:Receptors, Calcitonin / Q000378:metabolism*
chemical_list: D018003:Receptors, Calcitonin; D002118:Calcium