Evidence map›Paper›PMID 19172215›Full record

ArticleCalcified tissue international2009

Ablation of cathepsin k activity in the young mouse causes hypermineralization of long bone and growth plates.

Adele L Boskey, Bruce D Gelb, Eric Pourmand, Valery Kudrashov, Stephen B Doty, Lyudmila Spevak, Mitchell B Schaffler

Open access · greenAbstract read
In one paragraph

Article in Calcified tissue international, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.3field-weighted citation impact, top 20% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Impaired fracture healing in macrophage migration inhibitory factor-deficient mice.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2011
    Article
  10. Potential role of cathepsin K in the pathophysiology of mucopolysaccharidoses.Journal of pediatric rehabilitation medicine · 2010
    Article
  11. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Adele L BoskeyMusculoskeletal Integrity Program, Hospital for Special Surgery, New York, NY 10021, USA. boskeya@hss.edu
Bruce D Gelb
Eric Pourmand
Valery Kudrashov
Stephen B Doty
Lyudmila Spevak
Mitchell B Schaffler
Hospital for Special Surgery · USCity College of New York · USIcahn School of Medicine at Mount Sinai · US

Funding

Osteocyte Integrity and Bone RemodelingR01AR041210 · NIAMS · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI SCHAFFLER, MITCHELL B · 1997 to 2019
$5.8M
TRABECULAR BONE ADAPTATION TO MECHANICAL LOADINGP30AR046121 · NIAMS · HOSPITAL FOR SPECIAL SURGERY · PI MYERS, ELIZABETH R. · 1999 to 2010
$5.5M
IN VIVO INITIATION OF BIOLOGICAL CALCIFICATIONR01AR037661 · NIAMS · HOSPITAL FOR SPECIAL SURGERY · PI BOSKEY, ADELE L · 1987 to 2009
$2.8M
MICRODAMAGE AND BONE REMODELING IN STRESS FRACTURER29AR041210 · NIAMS · HENRY FORD HEALTH SYSTEM · PI SCHAFFLER, MITCHELL B · 1992 to 1996
–
NIAMS NIH HHS AR037661NIAMS NIH HHS AR046121NIAMS NIH HHS AR41210NIAMS NIH HHS P30 AR046121NIAMS NIH HHS R01 AR037661NIAMS NIH HHS R01 AR041210
6 · The paper itself

Abstract

Cathepsin K deficiency in humans causes pycnodysostosis, which is characterized by dwarfism and osteosclerosis. Earlier studies of 10-week-old male cathepsin K-deficient (knockout, KO) mice showed their bones were mechanically more brittle, while histomorphometry showed that both osteoclasts and osteoblasts had impaired activity relative to the wild type (WT). Here, we report detailed mineral and matrix analyses of the tibia of these animals based on Fourier transform infrared microspectroscopy and imaging. At 10 weeks, there was significant hypercalcification of the calcified cartilage and cortices in the KO. Carbonate content was elevated in the KO calcified cartilage as well as cortical and cancellous bone areas. These data suggest that cathepsin K does not affect mineral deposition but has a significant effect on mineralized tissue remodeling. Since growth plate abnormalities were extensive despite reported low levels of cathepsin K expression in the calcified cartilage, we used a differentiating chick limb-bud mesenchymal cell system that mimics endochondral ossification but does not contain osteoclasts, to show that cathepsin K inhibition during initial stages of mineral deposition retards the mineralization process while general inhibition of cathepsins can increase mineralization. These data suggest that the hypercalcification of the cathepsin K-deficient growth plate is due to persistence of calcified cartilage and point to a role of cathepsin K in bone tissue development as well as skeletal remodeling.

Indexed as

AnimalsBone DevelopmentCalcification, PhysiologicCalcinosisCathepsin KCathepsinsCell DifferentiationEnzyme InhibitorsGrowth PlateMaleMesodermMiceMice, Inbred C57BLMice, KnockoutOsteogenesisTibiaCathepsin KCathepsinsCTSK protein, humanCtsk protein, mouseEnzyme Inhibitors

Identifiers

PMID19172215
PMCPMC2680183
OpenAlexW2149265913

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.