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Cited by 7Bone Metabolism and DiseasesBone health and osteoporosis researchAlkaline Phosphatase Research Studies

Nemo‐Like Kinase Regulates Postnatal Skeletal Homeostasis

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Canalis, Ernesto, Kranz, Lauren, Zanotti, Stefano·2014·Journal of Cellular Physiology
DOI 10.1002/jcp.24625PMC PMC4117815
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Abstract

Nemo-like kinase (Nlk) is related to the mitogen-activated protein (MAP) kinases and known to regulate signaling pathways involved in osteoblastogenesis. In vitro Nlk suppresses osteoblastogenesis, but the consequences of the Nlk inactivation in the skeleton in vivo are unknown. To study the function of Nlk, Nlk(loxP/loxP) mice, where the Nlk exon2 is flanked by lox(P) sequences, were mated with mice expressing the Cre recombinase under the control of the paired-related homeobox gene 1 (Prx1) enhancer (Prx1-Cre), the Osterix (Osx-Cre) or the osteocalcin/bone gamma carboxyglutamate protein (Bglap-Cre) promoter. Prx1-Cre;Nlk(Δ/Δ) mice did not exhibit a skeletal phenotype except for a modest increase in trabecular number and connectivity observed only in 3-month-old male mice. Osx-Cre;Nlk(Δ/Δ) male and female mice exhibited an increase in trabecular bone volume secondary to an increased trabecular number at 3 months of age. Bone histomorphometry revealed a decrease in osteoclast number and eroded surface in male mice, and decreased osteoblast number and function in female mice. Expression of osteoprotegerin mRNA was increased in calvarial extracts, explaining the decreased osteoclast and osteoblast number. The conditional deletion of Nlk in mature osteoblasts (Bglap-Cre;Nlk(Δ/Δ) ) resulted in no skeletal phenotype in 1- to 6-month-old male or female mice. In conclusion, when expressed in undifferentiated osteoblasts, Nlk is a negative regulator of skeletal homeostasis possibly by targeting signals that regulate osteoclastogenesis and bone resorption.

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Cited by

Sorted by citations

Authors
Canalis, E., Kranz, L., & Zanotti, S.
Affiliations
  • University of Connecticut (US)
  • Saint Francis Hospital & Medical Center (US)
Corresponding author
Canalis, Ernesto
ORCID
Venue
Journal of Cellular Physiology
Publisher
Wiley
Published
2014-07-29
Volume
229
Issue
11
Pages
1736-1743
ISSN
  • 0021-9541 (ISSN-L)
  • 1097-4652
DOI
10.1002/jcp.24625
PMC
PMC4117815
OpenAlex
W1910428988
Cited by
7
References
2
Citations by year
2025: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 1
FWCI
0.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Cellular Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR063049)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK045227)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
Keywords
Nemo-like kinase, mitogen-activated protein kinase, skeletal homeostasis, osteoblastogenesis, osteoclastogenesis, bone resorption, trabecular bone, osteoprotegerin, conditional knockout mice, sex differences
MeSH terms
Sp7 Transcription Factor, Alleles, Animals, Animals, Newborn, Enzyme Activation, Female, Femur, Gene Expression Regulation, Homeostasis, Male, Mice, Inbred C57BL, Mice, Transgenic, Osteoblasts, RNA, Messenger, Skull, Transcription Factors, Protein Serine-Threonine Kinases, Gene Targeting, Muscle, Skeletal, Integrases, Mitogen-Activated Protein Kinases, Mice, Osteoprotegerin, RANK Ligand, X-Ray Microtomography

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