Date of Award
8-2016
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Bioengineering
Committee Member
Dr. Jeremy Mercuri, Committee Chair
Committee Member
Dr. William King
Committee Member
Dr. Martine LaBerge
Committee Member
Dr. Jennifer Woodell-May
Abstract
Osteoarthritis (OA) is a debilitating and painful disease that affects upwards of one in every eight adults1,2. OA influences the entire joint, but is traditionally characterized by cartilage degradation3. OA is a multifactorial disease with genetic, biological, and biochemical consideration, but there has been a recent shift in scientific opinion that the pathological progression of OA stems from an inflammatory milieu produced by the feed-forward progressive pathway as evidenced by simultaneous cartilage and synovium co-culture4–7. Autologous protein solution (APS) poses as an intriguing potential OA therapy by possessing a high anti-inflammatory and anabolic mediator concentration profile that could potentially mitigate the progression of OA8.
A human OA in vitro co-culture model with patient-matched cartilage and synovium was validated and used to analyze the effects of APS on OA progression. The outcome measures used to assess OA co-culture with and without APS included: cell viability, histological, and biochemical assays including enzyme-linked immunosorbent assays (ELISA) and dimethyl methylene blue (DMMB) assays. The co-culture model exhibited the hallmarks of OA including pathologically progressive cartilage destruction and the presence of inflammatory cytokines.
APS treatment showed encouraging results in mitigating OA as APS treated co-culture cartilage experienced less chondrocyte cloning and a general increase of anti-inflammatory mediators within the OA environment. Given these results, APS could be a promising OA mitigation therapy to evaluate further in in vivo trials.
1. Hunter DJ, Schofield D, Callander E. The individual and socioeconomic impact of osteoarthritis. Nat Rev Rheumatol. 2014;10(7):437-441. doi:10.1038/nrrheum.2014.44.
2. Musumeci G, Aiello F, Szychlinska M, Di Rosa M, Castrogiovanni P, Mobasheri A. Osteoarthritis in the XXIst Century: Risk Factors and Behaviours that Influence Disease Onset and Progression. Int J Mol Sci. 2015;16(3):6093-6112. doi:10.3390/ijms16036093.
3. Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012;64(6):1697-1707. doi:10.1002/art.34453.
4. Sutton S, Clutterbuck A, Harris P, et al. The contribution of the synovium, synovial derived inflammatory cytokines and neuropeptides to the pathogenesis of osteoarthritis. Vet J. 2009;179(1):10-24. doi:10.1016/j.tvjl.2007.08.013.
5. Dieppe PA, Lohmander LS. Pathogenesis and management of pain in osteoarthritis. Lancet. 2005;365(9463):965-973. doi:10.1016/S0140-6736(05)71086-2.
6. Topoluk N, Steckbeck K, Siatkowski S, Burnikel B, Tokish J, Mercuri J. Validation of an In Vitro Co-Culture Model Comprised of Human Osteoarthritic Joint Tissue Explants. In: Orthopaedic Research Society. Orlando, FL, USA; 2016.
7. Beekhuizen M, Bastiaansen-jenniskens YM, Koevoet W, et al. Osteoarthritic synovial tissue inhibition of proteoglycan production in human osteoarthritic knee cartilage: establishment and characterization of a long-term cartilage-synovium coculture. Arthritis Rheum. 2011;63(7):1918-1927. doi:10.1002/art.30364.
8. Woodell-May J, Matuska A, Oyster M, Welch Z, O’Shaughnessey K, Hoeppner J. Autologous protein solution inhibits MMP-13 production by IL-1β and TNFα-stimulated human articular chondrocytes. J Orthop Res. 2011;29(9):1320-1326. doi:10.1002/jor.21384.
Recommended Citation
Steckbeck, Kathleen Emily, "Autologous Protein Solution Exhibits Potential to Mitigate Osteoarthritis (OA) Progression in a Human Explant Co-Culture Model" (2016). All Theses. 3031.
https://tigerprints.clemson.edu/all_theses/3031