TY - JOUR
T1 - Stromal cell-derived factor-1 as a potential therapeutic target for osteoarthritis and rheumatoid arthritis
AU - Bragg, Robert
AU - Gilbert, William
AU - Elmansi, Ahmed M.
AU - Isales, Carlos M.
AU - Hamrick, Mark W.
AU - Hill, William D.
AU - Fulzele, Sadanand
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This publication is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research, and Development Program (VA Merit Award 1I01CX000930 01, W.D.H. and S.F.) and the National Institutes of Health (National Institute on Aging-AG036675 W.D.H., M.M.L., S.F., M.H. and C.S.). The contents of this publication do not represent the views of the Department of Veterans Affairs or the United States Government. The above-mentioned funding did not lead to any conflict of interests regarding the publication of this manuscript.
Funding Information:
SDF-1 is a cytokine that has been shown to have many different functions, from the anabolic effects of endochondral bone formation to playing a role in the development of both RA and OA. In RA, SDF-1 contributes to the migration of osteoclast precursor cells within the synovium as well as increasing cell size, TRAP activity, and preventing osteoclast apoptosis. Similarly, in OA, SDF-1 contributes to the degeneration of cartilage through the upregulation of proteolytic enzymes, such as aggrecanases and MMP-13, in addition to contributing to the induction of osteoblast proliferation. In proving that SDF-1 contributes to these degenerative diseases, it has a potential to be used as a therapeutic target. Several SDF-1–CXCR4 antagonists, such as AMD3100 and T140 have been shown to be beneficial in slowing the progression of subchondral bone loss by reduction in the formation of proteolytic enzymes, such as MMPs. Further studies need to be done to solidify the therapeutic effects in large animal models, which then can hopefully progress from the bench to bedside in patients with RA and OA. Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This publication is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research, and Development Program (VA Merit Award 1I01CX000930 01, W.D.H. and S.F.) and the National Institutes of Health (National Institute on Aging-AG036675 W.D.H., M.M.L., S.F., M.H. and C.S.). The contents of this publication do not represent the views of the Department of Veterans Affairs or the United States Government. The above-mentioned funding did not lead to any conflict of interests regarding the publication of this manuscript. Conflict of interest statement The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. ORCID iD Sadanand Fulzele https://orcid.org/0000-0002-3510-6759
Publisher Copyright:
© The Author(s), 2019.
PY - 2019
Y1 - 2019
N2 - With age, joints become subject to chronic inflammatory processes that lead to degeneration of articular cartilage. Although multifactorial, cytokines have been shown to play a role in the pathogenesis of these chronic disease states. Stromal cell-derived factor 1 (SDF-1) is a chemokine that has been shown to be active in homeostatic mechanisms and developmental processes throughout the body, such as endochondral bone formation. SDF-1 plays a role in the transition from cartilage to bone. Although it has been shown to be a factor in normal development, it has also been shown to involve in the pathogenesis of rheumatoid arthritis (RA) and osteoarthritis (OA). In RA, SDF-1 has been shown to stimulate the recruitment of proinflammatory cells, as well as osteoclasts to the synovium, aiding in the facilitation of synovial degradation. Similarly, in OA, SDF-1 has been shown to regulate key proteins involved in the degradation of the cartilage of the joint. Because of its role in degenerative joint disease, SDF-1 has been investigated as a potential therapeutic target. Animal studies have been employing SDF-1 inhibitors, such as AMD3100 and T140, to study their effects on attenuating degenerative joint disease. These studies have shown promising results in slowing the progression of cartilage degradation and could potentially be used as therapeutic target for humans OA and RA.
AB - With age, joints become subject to chronic inflammatory processes that lead to degeneration of articular cartilage. Although multifactorial, cytokines have been shown to play a role in the pathogenesis of these chronic disease states. Stromal cell-derived factor 1 (SDF-1) is a chemokine that has been shown to be active in homeostatic mechanisms and developmental processes throughout the body, such as endochondral bone formation. SDF-1 plays a role in the transition from cartilage to bone. Although it has been shown to be a factor in normal development, it has also been shown to involve in the pathogenesis of rheumatoid arthritis (RA) and osteoarthritis (OA). In RA, SDF-1 has been shown to stimulate the recruitment of proinflammatory cells, as well as osteoclasts to the synovium, aiding in the facilitation of synovial degradation. Similarly, in OA, SDF-1 has been shown to regulate key proteins involved in the degradation of the cartilage of the joint. Because of its role in degenerative joint disease, SDF-1 has been investigated as a potential therapeutic target. Animal studies have been employing SDF-1 inhibitors, such as AMD3100 and T140, to study their effects on attenuating degenerative joint disease. These studies have shown promising results in slowing the progression of cartilage degradation and could potentially be used as therapeutic target for humans OA and RA.
KW - osteoarthritis
KW - rheumatoid arthritis
KW - stromal cell-derived factor-1 (SDF1)
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U2 - 10.1177/2040622319882531
DO - 10.1177/2040622319882531
M3 - Review article
AN - SCOPUS:85074132685
SN - 2040-6223
VL - 10
JO - Therapeutic Advances in Chronic Disease
JF - Therapeutic Advances in Chronic Disease
ER -