ArticleLaboratory investigation; a journal of technical methods and pathology2012
Gene disruption of the calcium channel Orai1 results in inhibition of osteoclast and osteoblast differentiation and impairs skeletal development.
Article in Laboratory investigation; a journal of technical methods and pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 70 citations in OpenAlex.
- Pathological calcium overload impairs skeletal muscle regeneration through sustained NFAT-dependent proliferative signaling.Experimental & molecular medicine · 2026Article
- Spectrum and functions of ion channels and transporters in osteoclasts.Bone research · 2026Review
- Orai1 is Required for Osteogenic Differentiation on Nanoparticulate Mineralized Collagen Glycosaminoglycan Materials.Macromolecular bioscience · 2025Article
- Review
- Targeting TRPC channels for control of arthritis-induced bone erosion.Science advances · 2025Article
- Review
- Preclinical evaluation of ELP-004 in mice.Pharmacology research & perspectives · 2024Article
- Molecular Regulation of Bone Turnover in Juvenile Idiopathic Arthritis: Animal Models, Cellular Features and TNFα.Frontiers in bioscience (Landmark edition) · 2024Review
- Convergence of Calcium Channel Regulation and Mechanotransduction in Skeletal Regenerative Biomaterial Design.Advanced healthcare materials · 2023Review
- Article
- Calcium-Permeable Channels Cooperation for Rheumatoid Arthritis: Therapeutic Opportunities.Biomolecules · 2022Review
- Effects of D-Serine and MK-801 on Neuropathic Pain and Functional Recovery in a Rat Model of Spinal Cord Injury.Neurospine · 2022Article
- Calcium released by osteoclastic resorption stimulates autocrine/paracrine activities in local osteogenic cells to promote coupled bone formation.American journal of physiology. Cell physiology · 2022Article
- Role of KInternational journal of molecular sciences · 2021Review
- Article
- The function of the calcium channel Orai1 in osteoclast development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Calcium Transport in Specialized Dental Epithelia and Its Modulation by Fluoride.Frontiers in endocrinology · 2021Review
- ORAI1 CaFrontiers in cell and developmental biology · 2021Review
- Membrane Transport Proteins in Osteoclasts: The Ins and Outs.Frontiers in cell and developmental biology · 2021Review
- Finely-Tuned Calcium Oscillations in Osteoclast Differentiation and Bone Resorption.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Calcium signaling plays a central role in the regulation of bone cells, although uncertainty remains with regard to the channels involved. In previous studies, we determined that the calcium channel Orai1 was required for the formation of multinucleated osteoclasts in vitro. To define the skeletal functions of calcium release-activated calcium currents, we compared the mice with targeted deletion of the calcium channel Orai1 to wild-type littermate controls, and examined differentiation and function of osteoblast and osteoclast precursors in vitro with and without Orai1 inhibition. Consistent with in vitro findings, Orai1(-/-) mice lacked multinucleated osteoclasts. Yet, they did not develop osteopetrosis. Mononuclear cells expressing osteoclast products were found in Orai1(-/-) mice, and in vitro studies showed significantly reduced, but not absent, mineral resorption by the mononuclear osteoclast-like cells that form in culture from peripheral blood monocytic cells when Orai1 is inhibited. More prominent in Orai1(-/-) mice was a decrease in bone with retention of fetal cartilage. Micro-computed tomography showed reduced cortical ossification and thinned trabeculae in Orai1(-/-) animals compared with controls; bone deposition was markedly decreased in the knockout mice. This suggested a previously unrecognized role for Orai1 within osteoblasts. Analysis of osteoblasts and precursors in Orai1(-/-) and control mice showed a significant decrease in alkaline phosphatase-expressing osteoblasts. In vitro studies confirmed that inhibiting Orai1 activity impaired differentiation and function of human osteoblasts, supporting a critical function for Orai1 in osteoblasts, in addition to its role as a regulator of osteoclast formation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.