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Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone. It is believed to be the fourth leading cause of disability in the world, affecting 1 in 7 adults in the United States alone. The most common symptoms are joint pain and stiffness. Usually the symptoms progress slowly over years. Other symptoms may include joint swelling, decreased range of motion, and, when the back is affected, weakness or numbness of the arms and legs. The most commonly involved joints are the two near the ends of the fingers and the joint at the base of the thumbs, the knee and hip joints, and the joints of the neck and lower back. The symptoms can interfere with work and normal daily activities. Unlike some other types of arthritis, only the joints, not internal organs, are affected.
Glucosamine (C6H13NO5) is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine is part of the structure of two polysaccharides, chitosan and chitin. Glucosamine is one of the most abundant monosaccharides. Produced commercially by the hydrolysis of shellfish exoskeletons or, less commonly, by fermentation of a grain such as corn or wheat, glucosamine has many names depending on country.
Chondrocytes are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans. Although the word chondroblast is commonly used to describe an immature chondrocyte, the term is imprecise, since the progenitor of chondrocytes can differentiate into various cell types, including osteoblasts.
Chondrogenesis is the biological process through which cartilage tissue is formed and developed. This intricate and tightly regulated cellular differentiation pathway plays a crucial role in skeletal development, as cartilage serves as a fundamental component of the embryonic skeleton. The term "chondrogenesis" is derived from the Greek words "chondros," meaning cartilage, and "genesis," meaning origin or formation.
Bone morphogenetic protein 7 or BMP7 is a protein that in humans is encoded by the BMP7 gene.
Bone morphogenetic protein 2 or BMP-2 belongs to the TGF-β superfamily of proteins.
Bone morphogenetic protein 4 is a protein that in humans is encoded by BMP4 gene. BMP4 is found on chromosome 14q22-q23.
Bone morphogenetic protein 10 (BMP10) is a protein that in humans is encoded by the BMP10 gene.
Bone morphogenetic protein 5 is a protein that in humans is encoded by the BMP5 gene.
Bone morphogenetic protein 1, also known as BMP1, is a protein which in humans is encoded by the BMP1 gene. There are seven isoforms of the protein created by alternate splicing.
Bone morphogenetic protein 3, also known as osteogenin, is a protein in humans that is encoded by the BMP3 gene.
Growth differentiation factor 2 (GDF2) also known as bone morphogenetic protein (BMP)-9 is a protein that in humans is encoded by the GDF2 gene. GDF2 belongs to the transforming growth factor beta superfamily.
Growth/differentiation factor 5 is a protein that in humans is encoded by the GDF5 gene.
Growth differentiation factor 6 (GDF6) is a protein that in humans is encoded by the GDF6 gene.
The interleukin-1 receptor antagonist (IL-1RA) is a protein that in humans is encoded by the IL1RN gene.
Tiludronic acid is a bisphosphonate used for treatment of Paget's disease of bone in human being medicine. It has the tradename Skelid. In veterinary medicine, tiludronic acid is used to treat navicular disease and bone spavin in horses. Its tradenames are Tildren and Equidronate. It is approved for treatment of navicular disease and distal, tarsal osteoarthritis in Europe, and was approved for treatment of navicular disease in the United States in 2014.
An inflammatory cytokine or proinflammatory cytokine is a type of signaling molecule that is secreted from immune cells like helper T cells (Th) and macrophages, and certain other cell types that promote inflammation. They include interleukin-1 (IL-1), IL-6, IL-12, and IL-18, tumor necrosis factor alpha (TNF-α), interferon gamma (IFNγ), and granulocyte-macrophage colony stimulating factor (GM-CSF) and play an important role in mediating the innate immune response. Inflammatory cytokines are predominantly produced by and involved in the upregulation of inflammatory reactions.
Gene therapy for osteoarthritis is the application of gene therapy to treat osteoarthritis (OA). Unlike pharmacological treatments which are administered locally or systemically as a series of interventions, gene therapy aims to establish sustained therapeutic effect after a single, local injection.
The treatment of equine lameness is a complex subject. Lameness in horses has a variety of causes, and treatment must be tailored to the type and degree of injury, as well as the financial capabilities of the owner. Treatment may be applied locally, systemically, or intralesionally, and the strategy for treatment may change as healing progresses. The end goal is to reduce the pain and inflammation associated with injury, to encourage the injured tissue to heal with normal structure and function, and to ultimately return the horse to the highest level of performance possible following recovery.
A disease-modifying osteoarthritis drug (DMOAD) is a disease-modifying drug that would inhibit or even reverse the progression of osteoarthritis. Since the main hallmark of osteoarthritis is cartilage loss, a typical DMOAD would prevent the loss of cartilage and potentially regenerate it. Other DMOADs may attempt to help repair adjacent tissues by reducing inflammation. A successful DMOAD would be expected to show an improvement in patient pain and function with an improvement of the health of the joint tissues.
References
- 1 2 3 "Dr. Alicia Bertone is appointed Vice Provost for Graduate Studies and Dean of the Graduate School at Ohio State | College of Veterinary Medicine". vet.osu.edu.
- 1 2 "Alicia Bertone | College of Veterinary Medicine". vet.osu.edu.
- 1 2 "Alicia L Bertone". scholar.google.com.
- ↑ "Consortium for Advancement of Neuromusculoskeletal (NMS) Science and Locomotion (CANSL): Regeneration & Recovery (R&R)- A-1" (PDF).
- ↑ "OSU professor doesn't feel saddled by job helping horses". The Lantern. March 9, 1999.
- ↑ "New Ohio Laboratory to Benefit Horses, Humans, and Other Species". The Horse. August 1, 2002.
- ↑ Palmer, Jan L.; Bertone, Alicia L. (July 1994). "Joint structure, biochemistry and biochemical disequilibrium in synovitis and equine joint disease". Equine Veterinary Journal. 26 (4): 263–277. doi:10.1111/j.2042-3306.1994.tb04386.x. PMID 8575393.
- ↑ Bertone, A. L.; Palmer, J. L.; Jones, J. (December 2001). "Synovial fluid cytokines and eicosanoids as markers of joint disease in horses". Veterinary Surgery. 30 (6): 528–538. doi:10.1053/jvet.2001.28430. PMID 11704948.
- ↑ Doucet, Michèle Y.; Bertone, Alicia L.; Hendrickson, Dean; Hughes, Faith; MacAllister, Charles; McClure, Scott; Reinemeyer, Craig; Rossier, Yves; Sifferman, Roger; Vrins, André A.; White, Gary; Kunkle, Bruce; Alva, Roberto; Romano, Davida; Hanson, Peter D. (January 2008). "Comparison of efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis". Journal of the American Veterinary Medical Association. 232 (1): 91–97. doi:10.2460/javma.232.1.91. PMID 18167116.
- ↑ Santangelo, K.S.; Nuovo, G.J.; Bertone, A.L. (December 2012). "In vivo reduction or blockade of interleukin-1β in primary osteoarthritis influences expression of mediators implicated in pathogenesis". Osteoarthritis and Cartilage. 20 (12): 1610–1618. doi:10.1016/j.joca.2012.08.011. PMC 3478416 . PMID 22935786.
- ↑ Bertone, A. L.; Pittman, D. D.; Bouxsein, M. L.; Li, J.; Clancy, B.; Seeherman, H. J. (November 2004). "Adenoviral-mediated transfer of human BMP-6 gene accelerates healing in a rabbit ulnar osteotomy model". Journal of Orthopaedic Research. 22 (6): 1261–1270. doi: 10.1016/j.orthres.2004.03.014 . PMID 15475207. S2CID 20793369.
- ↑ Zachos, Terri A.; Shields, Kathleen M.; Bertone, Alicia L. (June 2006). "Gene-mediated osteogenic differentiation of stem cells by bone morphogenetic proteins-2 or -6". Journal of Orthopaedic Research. 24 (6): 1279–1291. doi:10.1002/jor.20068. PMID 16649180. S2CID 31060102.
- ↑ Zachos, Terri; Diggs, Alisha; Weisbrode, Steven; Bartlett, Jeffrey; Bertone, Alicia (August 2007). "Mesenchymal Stem Cell-mediated Gene Delivery of Bone Morphogenetic Protein-2 in an Articular Fracture Model". Molecular Therapy. 15 (8): 1543–1550. doi: 10.1038/sj.mt.6300192 . PMID 17519894.
- ↑ Menendez, M.I.; Clark, D.J.; Carlton, M.; Flanigan, D.C.; Jia, G.; Sammet, S.; Weisbrode, S.E.; Knopp, M.V.; Bertone, A.L. (August 2011). "Direct delayed human adenoviral BMP-2 or BMP-6 gene therapy for bone and cartilage regeneration in a pony osteochondral model". Osteoarthritis and Cartilage. 19 (8): 1066–1075. doi: 10.1016/j.joca.2011.05.007 . PMID 21683796.
- ↑ Waselau, M.; Sutter, W. W.; Genovese, R. L.; Bertone, A. L. (2008). "Intralesional injection of platelet-rich plasma followed by controlled exercise for treatment of midbody suspensory ligament desmitis in Standardbred racehorses". Journal of the American Veterinary Medical Association. 232 (10): 1515–1520. doi:10.2460/javma.232.10.1515. PMID 18479242.
- ↑ "Charles C. Capen Teaching Excellence Award for Graduate Education | College of Veterinary Medicine". vet.osu.edu.
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