title: RCANs regulate the convergent roles of NFATc1 in bone homeostasis.
abstract: Activation of calcineurin-dependent nuclear factor of activated T cells c1 (NFATc1) is convergent for normal bone homeostasis. NFATc1 regulates both osteoclastogenesis and osteoblastogenesis. Here we investigated the roles of regulator of calcineurin (RCAN) genes in bone homeostasis. RCANs function as potent physiological inhibitors of calcineurin. Overexpression of RCANs in osteoclast precursor cells attenuated osteoclast differentiation, while their overexpression in osteoblasts enhanced osteoblast differentiation and function. Intriguingly, opposing effects of RCANs in both cell types were shown by blocking activation of the calcineurin-NFATc1 pathway. Moreover, the disruption of RCAN1 or RCAN2 in mice resulted in reduced bone mass, which is associated with strongly increased osteoclast function and mildly reduced osteoblast function. Taken together, RCANs play critical roles in bone homeostasis by regulating both osteoclastogenesis and osteoblastogenesis, and they serve as inhibitors for calcineurin-NFATc1 signaling both in vivo and in vitro.
authors.affiliation: Department of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.|Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
authors.forename: Jung Ha
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
authors.forename: Kabsun
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
authors.forename: Inyoung
authors.initials: I
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.|Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
authors.forename: Semun
authors.initials: S
authors.lastname: Seong
authors.affiliation: Department of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.|Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Jeong
authors.affiliation: Department of Anatomy, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
authors.forename: Kwang-Il
authors.initials: KI
authors.lastname: Nam
authors.affiliation: Department of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
authors.forename: Kyung Keun
authors.initials: KK
authors.lastname: Kim
authors.affiliation: Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati, Cincinnati 45247, OH, USA.
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Molkentin
authors.affiliation: Department of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.|Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
authors.forename: Nacksung
authors.initials: N
authors.lastname: Kim
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000378:metabolism*; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000172:deficiency / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism*; D009929:Organ Size; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D011506:Proteins / Q000378:metabolism*; D053245:RANK Ligand / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D002135:Calcium-Binding Proteins; C511512:DSCR1 protein, mouse; C486303:Dscr1l1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D050778:NFATC Transcription Factors; D011506:Proteins; D053245:RANK Ligand