Sc65 is a novel endoplasmic reticulum protein that regulates bone mass homeostasis

Katrin Gruenwald, Patrizio Castagnola, Roberta Besio, Milena Dimori, Yuqing Chen, Nisreen S. Akel, Frances L. Swain, Robert A. Skinner, David R. Eyre, Dana Gaddy, Larry J. Suva, Roy Morello

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Members of the Leprecan family of proteins include enzymes, prolyl 3-hydroxylase 1 (P3h1), P3h2, and P3h3, and nonenzymatic proteins, Crtap and Sc65. Mutations in CRTAP and LEPRE1 (encoding P3H1) have been associated with human disease such as recessive osteogenesis imperfecta; however, the function of Sc65, which is closely related and highly homologous to Crtap, is unknown. Sc65 has been described as a synaptonemal complex protein, a nucleolar protein, and a cytoplasmic adapter protein. In light of its high sequence similarity with Crtap, an endoplasmic reticulum (ER)-associated protein, and the importance of post-translational modifications such as collagen prolyl 3-hydroxylation in bone metabolism, we hypothesized that Sc65 was an ER-resident protein that would have an important role in bone homeostasis. In this study, we demonstrate that Sc65 is a previously unrecognized ER protein and that it does not localize in the nucleus of somatic cells. Moreover, Sc65 is expressed and functional during skeletal development because loss of Sc65 results in a progressive osteopenia that affects both trabecular and cortical bone. Bone loss is the result of increased bone resorption mediated by a non-cell-autonomous effect on osteoclasts. Therefore, Sc65, like its related family member Crtap, is an important modulator of bone homeostasis, acting as a negative regulator of osteoclastogenesis.

Original languageEnglish
Pages (from-to)666-675
Number of pages10
JournalJournal of Bone and Mineral Research
Volume29
Issue number3
DOIs
Publication statusPublished - Mar 2014

Fingerprint

Endoplasmic Reticulum
Homeostasis
Bone and Bones
Proteins
Synaptonemal Complex
Osteogenesis Imperfecta
Metabolic Bone Diseases
Osteoclasts
Hydroxylation
Post Translational Protein Processing
Bone Resorption
Nuclear Proteins
Cell Nucleus
Osteogenesis
Collagen
Mutation
Enzymes

Keywords

  • bone
  • Crtap
  • endoplasmic reticulum
  • osteoclasts
  • osteogenesis imperfecta
  • SC65

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Sc65 is a novel endoplasmic reticulum protein that regulates bone mass homeostasis. / Gruenwald, Katrin; Castagnola, Patrizio; Besio, Roberta; Dimori, Milena; Chen, Yuqing; Akel, Nisreen S.; Swain, Frances L.; Skinner, Robert A.; Eyre, David R.; Gaddy, Dana; Suva, Larry J.; Morello, Roy.

In: Journal of Bone and Mineral Research, Vol. 29, No. 3, 03.2014, p. 666-675.

Research output: Contribution to journalArticle

Gruenwald, K, Castagnola, P, Besio, R, Dimori, M, Chen, Y, Akel, NS, Swain, FL, Skinner, RA, Eyre, DR, Gaddy, D, Suva, LJ & Morello, R 2014, 'Sc65 is a novel endoplasmic reticulum protein that regulates bone mass homeostasis', Journal of Bone and Mineral Research, vol. 29, no. 3, pp. 666-675. https://doi.org/10.1002/jbmr.2075
Gruenwald, Katrin ; Castagnola, Patrizio ; Besio, Roberta ; Dimori, Milena ; Chen, Yuqing ; Akel, Nisreen S. ; Swain, Frances L. ; Skinner, Robert A. ; Eyre, David R. ; Gaddy, Dana ; Suva, Larry J. ; Morello, Roy. / Sc65 is a novel endoplasmic reticulum protein that regulates bone mass homeostasis. In: Journal of Bone and Mineral Research. 2014 ; Vol. 29, No. 3. pp. 666-675.
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AU - Akel, Nisreen S.

AU - Swain, Frances L.

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