- Title Information
- Title
- Preventing Biological Wear in the Synovial Joint: The Role of Lubricin as a Boundary Lubricant and Tribosupplement
- Name:
Personal
- Name Part
- Waller, Kimberly A
- Role
- Role Term:
Text
- creator
- Origin Information
- Copyright Date
- 2013
- Physical Description
- Extent
- 27, 251 p.
- digitalOrigin
- born digital
- Note
- Thesis (Ph.D. -- Brown University (2013)
- Name:
Personal
- Name Part
- Jay, Gregory
- Role
- Role Term:
Text
- Director
- Name:
Personal
- Name Part
- Crisco, Joseph
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Darling, Eric
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Fleming, Braden
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Elsaid, Khaled
- Role
- Role Term:
Text
- Reader
- Name:
Corporate
- Name Part
- Brown University. Biomedical Engineering
- Role
- Role Term:
Text
- sponsor
- Genre (aat)
- theses
- Subject
- Topic
- lubricin
- Subject
- Topic
- PRG4
- Subject
- Topic
- chondrocyte apoptosis
- Subject
- Topic
- boundary lubrication
- Subject
- Topic
- cartilage mechanics
- Subject
- Topic
- camptodactyly-arthropathy-coxa vara-pericarditis syndrome
- Subject (FAST)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/817187")
- Topic
- Articular cartilage
- Subject (FAST)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/1048766")
- Topic
- Osteoarthritis
- Record Information
- Record Content Source (marcorg)
- RPB
- Record Creation Date
(encoding="iso8601")
- 20131219
- Language
- Language Term:
Code (ISO639-2B)
- eng
- Language Term:
Text
- English
- Abstract
- Articular cartilage is a smooth, load bearing tissue that lines the ends of bones in articulating joints. Smooth joint motion is facilitated by synovial fluid, which contains the lubricating factors lubricin and hyaluronic acid. While healthy articular cartilage can sustain decades of use, a variety of common risk factors, including age, obesity and injury, predispose many patients to degenerative joint diseases, including osteoarthritis (OA), which is characterized by joint pain, loss of motion and cartilage loss. Although OA is a widespread disease, treatment options are limited to pain management and total joint replacement. <br/><br/>
Lubricin is a mucinous glycoprotein produced by synovial cells and chondrocytes that forms a layer of molecules over the surface of healthy cartilage, providing boundary lubrication and chondroprotection to articulating joints. In its absence, articular cartilage experiences elevated friction and subsequent mechanical and biological damage.<br/><br/>
This work investigates the efficacy of lubricin to prevent both mechanical and biological wear of articular cartilage, using in vitro, in vivo and ex vivo models. We developed an in vitro cartilage lubrication and wear testing regimen that allows for subsequent cell culture and observation of the cellular response to friction and wear, which facilitates the testing of lubricants and therapeutics to evaluate OA treatments and prevention, and can be used to study different cartilaginous bearings in order to observe the lubrication and wear response in compromised tissues. In addition, we used animal models to investigate exogenous and endogenous tribosupplementation of lubricin, which provide insight into the treatment of degenerative joint diseases. <br/><br/>
In this dissertation, we show that lubricin is vital to boundary lubrication and the preservation of joint health at both the structural and cellular levels. Furthermore, we show that tribosupplementation provides joint lubrication and prevents apoptosis of chondrocytes in lubricin deficient disease models.<br/><br/>
The major findings in this dissertation support further investigation of lubricin as a tribosupplenent in large animal preclinical models and in patients with genetic or acquired lubricin deficiency, who have unmet medical needs. Furthermore, this work provides insight into the mechanopathway relating friction and apoptosis, which provides groundwork for additional therapeutic targets in the prevention of biological wear.
- Identifier:
DOI
- 10.7301/Z0S180TB
- Access Condition:
rights statement
(href="http://rightsstatements.org/vocab/InC/1.0/")
- In Copyright
- Access Condition:
restriction on access
- Collection is open for research.
- Type of Resource (primo)
- dissertations