Research News

David Eyre, PhD
David Eyre, PhD
David Hudson, PhD
Dave Hudson, PhD

David Eyre, PhD and David Hudson, PhD in the Collagen Biology and Genetic Disorders Lab gave the following presentations at 1st MBE (Matrix Biology Europe) conference (XXIVth FECTS meeting) in Rotterdam, the Netherlands on June 21-24, 2014:

David Eyre Plenary Lecture:
"Molecular sites, diversity and biological consequences of collagen cross-links"

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Bot­u­linum toxin induces mus­cle paral­y­sis and inhibits bone regen­er­a­tion in zebrafish

Congratulations to the Musculoskeletal Systems Biology Lab (MSBL) and Orthopaedic Science Laboratories (OSL) who just had the following paper pub­lished online in the Jour­nal of Bone and Min­eral Research!

Bot­u­linum toxin induces mus­cle paral­y­sis and inhibits bone regen­er­a­tion in zebrafish

Recidoro AM, Roof AC, Schmitt M, Worton LE...

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Adrian Monstad-RiosCongrats to Musculoskeletal Systems Biology Lab (MSBL) member Adrian Monstad-Rios who has been accepted to the Washington NASA Space Grant Consortium Summer Undergraduate Research Program (SURP)!

SURP offers undergraduates the opportunity to work in a science, technology, engineering or mathematics research position that...

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Epigenetic regulation of articular joints

UW Orthopaedics and Sports Medicine faculty, staff, residents and medical students will be presenting at the Orthopaedic Research Society (ORS) 2014 Annual Meeting in New Orleans on March 15-18. The following is a selection of the papers and posters being presented by our department.

ESET Histone Methyltransferase Regulates Terminal Differentiation Of Articular Chondrocytes

Kevin A. Lawson, Colin J. Teteak, Junhui Zou, Jacques Hacquebord, Andrew Ghatan, Anna Zielinska-Kwiatkowska, Russell J. Fernandes, Howard A. Chansky, Liu Yang
The first author Kevin A. Lawson (a 4th year medical student working in the Molecular Orthopaedics Lab) has been selected as the finalist for New Investigator Recognition Award at this meeting.

ESET Histone Methyltransferase Is Required For Postnatal Development And Maintenance Of The Cruciate Ligaments

Michael J. Chen, Sean Haloman, M.D., John W. McCornack, Daniel J. Leong, Hui B. Sun, Ph.D., Howard A. Chansky, M.D., Liu Yang, Ph...

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Featured Articles

Ulbrecht JS, Hurley T, Mauger DT, Cavanagh PR.

In a recent publication of Diabetes Care, Department of Orthopaedics and Sports Medicine Faculty member Peter Cavanagh assessed the efficacy of in-shoe orthoses that were designed based on shape and barefoot plantar pressure in reducing the incidence of submetatarsal head plantar ulcers in people with diabetes, peripheral neuropathy, and a history of similar prior ulceration.

In a single-blinded multicenter randomized controlled trial, subjects were randomized to wear shape- and pressure-based orthoses (experimental, n = 66) or standard-of-care A5513 orthoses (control, n = 64). Patients were followed for 15 months, until a study end point (forefoot plantar ulcer or nonulcerative plantar forefoot lesion) or to study termination. Proportional hazards regression was used for analysis.

There was a trend in the composite primary end point (both ulcers and nonulcerative lesions) across the full follow-up period (P = 0.13) in favor of the...

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Schmale GA, Kweon C, Larson RV, Bompadre V.
Clin Orthop Relat Res. 2014 Jul;472(7):2168-74. doi: 10.1007/s11999-014-3561-6. Epub 2014 Mar 15.

UW Orthopaedics and Sports Medicine faculty members performed a retrospective review of 29 patients who underwent transphyseal ACL reconstruction using soft tissue grafts passed through open physes and followed to skeletal maturity, and at least 2 years from their index surgery, who were invited and returned for a study interview and examination. Pre- and postinjury activity levels were assessed via the Tegner activity score, satisfaction was determined using a 10-point Likert scale, function was assessed via the Lysholm score and IKDC grade, and an open-ended questionnaire was used for explanations of changes in activity levels. Reoperations were classified as major or minor, determined from a review of the medical records conducted after interview and examination.

At a minimum follow up of 2 years (mean, 4 years; range, 2-8 years), four revision reconstructions and seven minor operations were performed for a reoperation rate of 11 of 29 (38%). Eight of 29...

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Gundle KR, Cizik AM, Punt SE, Conrad EU 3rd, Davidson DJ.
Sarcoma. 2014;2014:450902. doi: 10.1155/2014/450902. Epub 2014 Mar 19.

In a recent publication in Sarcoma, UW Orthopaedics faculty, staff, and residents,sought to describe a psychometric evaluation of the SF-6D in a cross-sectional population of lower extremity sarcoma patients.

In 63 pairs of surveys in a lower extremity sarcoma population, the mean preference-weighted SF-6D score was 0.59 (95% CI 0.4-0.81). The distribution of SF-6D scores approximated a normal curve (skewness = 0.11). There was a positive correlation between the SF-6D and TESS (r = 0.75, P < 0.01). Respondents who reported walking aid use had lower SF-6D scores (0.53 versus 0.61, P = 0.03). Five respondents underwent amputation, with lower SF-6D scores that approached significance (0.48 versus 0.6, P = 0.06).

The SF-6D health state utilities measure demonstrated convergent validity without evidence of ceiling or...

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Recidoro AM, Roof AC, Schmitt M, Worton LE, Petrie T, Strand N, Ausk BJ, Srinivasan S, Moon RT, Gardiner EM, Kaminsky W, Bain SD, Allan CH, Gross TS, Kwon RY.
J Bone Miner Res. 2014 May 7. doi: 10.1002/jbmr.2274. [Epub ahead of print]

In a recent article in the Journal of Bone and Mineral Research, researchers from the Orthopaedics Research Lab  developed a model of Botulinum toxin (BTx)-induced muscle paralysis in adult zebrafish and examined its effects on intramembranous ossification during tail fin regeneration.

Intramuscular administration of BTx has been associated with impaired osteogenesis in diverse conditions of bone formation (e.g., development, growth, and healing), yet the mechanisms of neuromuscular-bone crosstalk underlying these deficits have yet to be identified. Motivated by the emerging utility of zebrafish (Danio rerio) as a rapid, genetically tractable, and optically transparent model for human pathologies (as well as the potential to interrogate neuromuscular-mediated bone disorders in a simple model...

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Kollitz KM, Parsons EM, Weaver MS, Huang JI.
Hand (N Y). 2014 Jun;9(2):217-24. doi: 10.1007/s11552-013-9583-9.

A team of researchers at the Department of Orthopaedics and Sports Medicine—led by faculty member, Jerry Huang, and visiting medical student Katie Kollitz —has evaluated the effect of Platelet-rich plasma (PRP) on healing in a rabbit zone II flexor tendon model.  PRP has previously shown promise in the treatment of tendinopathy, including rotator cuff and lateral epicondylitis.

There were no significant differences in ultimate tensile strength between treatments at 2, 4, or 8 weeks. There was a trend towards lower tensile strength in the PRP group at 2 weeks. There was no statistically significant difference in excursion or range of motion between PRP and control tendons. Cell counts at 4 weeks were statistically significantly reduced in the PRP tendons as compared to controls. No difference in collagen content or maturity was detected.

In contrast to previous studies, PRP did not significantly improve ultimate tensile strength. PRP-...

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Kim JE, Lee SM, Kim SH, Tatman P, Gee AO, Kim DH, Lee KE, Jung Y, Kim SJ.
Int J Nanomedicine. 2014 May 7;9 Suppl 1:141-57. doi: 10.2147/IJN.S54114. eCollection 2014.

In a recent article, faculty member Albert Gee and his colleagues from the Department of Orthopaedics and Sports Medicine evaluated the efficacy of mesenchymal stem cells (MSCs) encapsulated in self-assembled peptide (SAP) hydrogels in a rat knee model for the prevention of osteoarthritis (OA) progression.

Concentration of biotinylated SAP at week 1 was not significantly different from those at week 3 and week 6 (P=0.565). Bone mineral density was significantly lower in SAP-MSC groups than controls (P=0.002). Significant differences in terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining between the control group and all other groups were observed. Caspase-8, tissue inhibitor of metalloproteinases 1, and matrix metalloproteinase 9 were diffusely stained in controls, whereas localized or minimal staining was observed in other groups. Modified Mankin scores were significantly lower in the SAP and SAP-MSC groups...

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Bone marrow- or vessel wall-derived osteoprotegerin is sufficient to reduce atherosclerotic lesion size and vascular calcification. Callegari A, Coons ML, Ricks JL, Yang HL, Gross TS, Huber P, Rosenfeld ME, Scatena M. Arterioscler Thromb Vasc Biol. 2013 Nov;33(11):2491-500. doi: 10.1161/ATVBAHA.113.301755. Epub 2013 Aug 29. PMID: 23990207

Vascular calcification refers to the mineralization of ectopic soft tissue in the walls of vessels in the vasculature system.  Of most concern is arterial wall mineralization, which is present in a majority of patients affected by cardiovascular disease. Osteoprotegerin (OPG) is a protein known to be involved in regulating bone homeostasis but has also been shown to play a controversial role in vascular calcification.  Researchers at the UW’s Department of Orthopaedics and Sports Medicine and Department of Bioengineering have found that OPG can strongly inhibit calcium...

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Burst fractures of the lumbar spine in frontal crashes

Kaufman RP, Ching RP, Willis MM, Mack CD, Gross JA, Bulger EM. Accid Anal Prev. 2013 Oct;59:153-63. doi: 10.1016/j.aap.2013.05.023. Epub 2013 Jun 3. PMID: 2379261

Researchers at the Harborview Injury Prevention and Research Center examined the types of motor vehicle accidents that can cause major compression lumbar spine (MCLS) fractures.  Compression and burst fractures of the lumbar spine are defined as a > 20% loss in height.  In the US, these types of injuries continue to occur despite improvements in restraint technology.  Researchers examined databases from the National Automative Sampling System (NASS) and Crash Injury Research and Engineering Network (CIREN) to examine biomechanical data and mechanism of injury for patients who have suffered MCLS fractures.  Study investigators found that frontal...

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ESET histone methyltransferase is essential to hypertrophic differentiation of growth plate chondrocytes and formation of epiphyseal plates
Yang L, Lawson KA, Teteak CJ, Zou J, Hacquebord J, Patterson D, Ghatan AC, Mei Q, Zielinska-Kwiatkowska A, Bain SD, Fernandes RJ, Chansky HA. Dev Biol. 2013 May 4. doi:pii: S0012-1606(13)00225-X. 10.1016/j.ydbio.2013.04.031. [Epub ahead of print] PMID: 23652029

 A team of researchers at the Department of Orthopaedics and Sports Medicine—led by faculty member, Liu Yang—have discovered that the protein ESET is fundamentally important in skeletal development.  ESET is a histone methyltransferase that catalyzes methylation of histones on DNA.  Their study used knock-out mice that were deficient in the ESET protein.  Comparisons with wild type mice found several key differences in the knock-out mice: 1) chondroctyes rapidly underwent hypertrophy, depleting...

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Bone Collagen: New Clues to Its Mineralization Mechanism from Recessive Osteogenesis Imperfecta. Eyre DR, Weis MA. Calcif Tissue Int. 2013 Mar 19. [Epub ahead of print] PMID: 23508630

 

In this review article, Dr. David Eyre and Mary Ann Weis (part of the Collagen Biology and Genetic Disorders Lab) discuss the mechanism behind bone collagen mineralization by examining recent findings about the genetic disorder osteogensis imperfecta.

Osteogenesis Imperfecta (OI) is a congenital bone disorder that is commonly known as “brittle bone disease.”  OI causes bones to fracture easily; it can cause loose joints, short stature and severe bone deformation.   It is caused by the inadequate formation of collagen—an important protein structure that creates the matrix on which...

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Comparison of Dry-Land Training Programs Between Age Groups of Swimmers
Krabak BJ, Hancock KJ, Drake S. PM R. 2013 Jan 29. doi:pii: S1934-1482(12)01710-8. 10.1016/j.pmrj.2012.11.003. PMID: 23375633

 

 

Faculty member Dr. Brian J. Krabak led a study that describes the use of dry-land training in swimmer athletes.  Traditionally, dry-land training has been used to enhance performance in the water and prevent injuries.  However, there is conflicting data that shows that these benefits actually exist.  By first establishing a description of the current use of dry land training by swim coaches, this can help establish future studies that examine the proposed benefits of this type of training.

 

Click here to view the complete article.

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White KK, Sousa T., J Am Acad Orthop Surg. 2013 Jan;21(1):12-22. doi: 10.5435/JAAOS-21-01-12. PMID: 23281467

 UW Orthopaedics and Sports Medicine faculty, Klane White, and resident, Ted Sousa, published a review article about a rare family of genetic disorders, mucopolysaccharidoses (MPSs).  There are seven distinct types of MPS that show similar clinical symptoms but range in severity.  MPSs are disorders characterized by the cell’s inability to degrade glycoaminoglycans (GAGs), long chains of sugar molecules that are the normal byproducts of cells.  This inability is attributed to the lack of or malfunction of lysosomal enzymes that normally serve to break these byproducts down.  Since the body is no longer able to break down GAGs, these accumulate in cells, disrupt normal cellular function and have a system wide effect on mental development, physical appearance and organ function. 

 According to the authors, skeletal abnormalities are early and prominent features of MPS, and the orthopaedic surgeon is often the first healthcare provider to raise suspicion for this diagnosis.  So it is important for orthopaedic surgeons...

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Baumann angle and radial-ulnar overlap: a radiographic study to control for the angle of the x-ray beam.
J. Lee Pace, MD, Brett Wiater, MD, Gregory Schmale, MD, Thomas Jinguji, MD, Viviana Bompadre, PhD, and Walter Krengel III, MD.  Department of Orthopedics and Sports Medicine, Seattle Children’s Hospital, University of Washington, Seattle, WA. J Pediatr Orthop. 2012 Jul-Aug;32(5):467-72. PMID: 22706461

 

UW Orthopaedic Faculty at Seattle Children’s Hospital wanted to investigate if there was any “surrogate” measure that could control for the angle of x-ray beams when examining Baumann’s angle.  Baumann’s angle (BA) is the most common radiographic measurement used to assess the alignment of the distal humerus and an abnormal BA can indicate to a physician a possible deformity in the distal humerus.  The angle at which the x-ray beam is positioned has an effect on the Baumann’s angle, as another paper...

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Type III collagen, a fibril network modifier in articular cartilage
Wu JJ, Weis MA, Kim LS, Eyre DR
J Biol Chem. 2010 Jun 11;285(24):18537-4


In a recent article in the Journal of Biological Chemistry, David Eyre and colleagues Maryann Weiss, Lannie Kim, and James Wu describe the role of type III collagen. This protein is synthesized in mature articular cartilage, as a covalent modifier  that may add cohesion to a weakened, existing collagen type II fibril network as part of a chondrocyte healing response to matrix damage. In the articular cartilages of adult joints, type III collagen makes an appearance in varying amounts superimposed on the original collagen fibril network. In a study to understand better the structural role of type III collagen in cartilage, the researchers found that type III collagen molecules with unprocessed N-propeptides are present in the extracellular matrix of adult human and bovine articular cartilages as covalently crosslinked polymers...
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01/20/2011
Comparison of one and two-stage revision of total hip arthroplasty complicated by infection: a markov expected-utility decision analysis. Wolf CF, Gu NY, Doctor JN, Manner PA, Leopold SS. J Bone Joint Surg Am. 2011 Apr;93(7):631-9. PMID: 21471416

Department of Orthopaedics and Sports Medicine Faculty members Seth Leopold and Paul Manner together used Markov modeling to study approaches to revision of total hip arthroplasty. Two-stage revisions complicated by chronic infection result in reinfection rates that are lower than those following single-stage revisions but may also result in increased surgical morbidity. Using a decision analysis, they compared single-stage and two-stage revisions to determine which treatment modality resulted in greater quality-adjusted life years (QALYs).


A review of the literature on the treatment of patients with an infection at the site of a total hip arthroplasty provided probabilities; utility values for common...

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Risk Factors for Medical Complication After Lumbar Spine Surgery: A Multivariate Analysis of 767 Patients. Lee, Michael J. MD; Hacquebord, Jacques MD; Varshney, 
Anuj MD; Cizik, Amy M. MPH; Bransford, Richard J. MD; Bellabarba, Carlo MD; Konodi, Mark A. MS; Chapman, Jens MD 
PMID:22046614 

Spine Surgery graphMany prior studies of complications during spine surgery have been done utilizing large national databases (e.g. Medicare and the National Inpatient Sample (NIS)). Although these allow for analysis of thousands of patients, potentially influential covariates are not...
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