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020 ▼a 9781392708903
035 ▼a (MiAaPQ)AAI27668436
040 ▼a MiAaPQ ▼c MiAaPQ ▼d 247004
0820 ▼a 574
1001 ▼a Stefani, Robert M.
24510 ▼a Role of the Synovial Membrane in Osteoarthritis Pathogenesis and Cartilage Repair.
260 ▼a [S.l.]: ▼b Columbia University., ▼c 2020.
260 1 ▼a Ann Arbor: ▼b ProQuest Dissertations & Theses, ▼c 2020.
300 ▼a 245 p.
500 ▼a Source: Dissertations Abstracts International, Volume: 81-06, Section: B.
500 ▼a Advisor: Hung, Clark.
5021 ▼a Thesis (Ph.D.)--Columbia University, 2020.
506 ▼a This item must not be sold to any third party vendors.
520 ▼a Osteoarthritis (OA) affects an estimated 250 million people worldwide, representing an enormous economic and social burden across demographic groups. While classically attributed to 'wear and tear' of the articular cartilage, there is a growing appreciation that OA is a whole-joint disease with a complex etiology involving the synovium and surrounding tissues. The synovium is a specialized connective tissue membrane that envelops the diarthrodial joint and maintains the synovial fluid environment through molecular secretion as well as bi-directional filtration of these constituents, nutrients, and cellular waste products. Moreover, synovium-derived cells have been directly implicated in both the native repair response as well as degradation of articular cartilage.Much of the existing research of synovium has been conducted in the context of rheumatoid arthritis (RA). And while synovitis is a key feature of both RA and OA, clinical reports have described OA synovium as distinct in its cellular and structural composition, molecular secretion, and chronic onset. However, literature studies have not adequately addressed the mechanisms by which alterations in synovium structure-function affect joint and cartilage health, particularly the contribution of different cell types within the synovium to solute transport and lubrication. The work described in this dissertation addresses these knowledge gaps in the context of existing and emerging OA therapies, namely glucocorticoids and electrical stimulation.We anticipate that a more comprehensive characterization of changes to the synovium composition, secretion of key metabolic mediators, lubrication properties, as well as its ability to regulate solute transport in and out of the joint space will not only contribute to our basic science understanding of the synovium but also the development and modification of therapeutic strategies aimed at restoring and maintaining joint health. This characterization will be facilitated by our laboratory's expertise in tissue engineering and explant culture, IL-1 and DEX stimulation, and electrical stimulation of joint tissues. The approach of using an engineered synovium model is attractive in that quantitative high throughput in vitro mechanistic studies can be performed on tissues that are fabricated from cells derived from normal and OA synovium of patients and corresponding immune cells at defined density and cell type ratios. It also facilitates isolating effects of certain cell types or starting composition that are found in explant specimens.Intra-articular glucocorticoid injections are commonly administered to patients in an effort to control inflammation and pain. And while these high dose injections are known to have significant detrimental local and systemic effects, comparatively low doses of dexamethasone (DEX), a synthetic glucocorticoid, are known to have pro-anabolic and anti-catabolic effects on cartilage cultures. Our laboratory has published extensively on the benefits of DEX stimulation in growth and maintenance of engineered and explanted cartilage as well as chondroprotection from pro-inflammatory cytokines (e.g interleukin-1
590 ▼a School code: 0054.
650 4 ▼a Biomedical engineering.
650 4 ▼a Mechanical engineering.
650 4 ▼a Biology.
690 ▼a 0541
690 ▼a 0548
690 ▼a 0306
71020 ▼a Columbia University. ▼b Biomedical Engineering.
7730 ▼t Dissertations Abstracts International ▼g 81-06B.
773 ▼t Dissertation Abstract International
790 ▼a 0054
791 ▼a Ph.D.
792 ▼a 2020
793 ▼a English
85640 ▼u http://www.riss.kr/pdu/ddodLink.do?id=T15494652 ▼n KERIS ▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다.
980 ▼a 202002 ▼f 2020
990 ▼a ***1816162
991 ▼a E-BOOK