{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T11:25:57Z","timestamp":1743161157339,"version":"3.37.3"},"reference-count":63,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["International Journal of Inflammation"],"published-print":{"date-parts":[[2022,6,2]]},"abstract":"<jats:p>Background. The loss of muscle mass in rheumatoid arthritis (RA), termed rheumatoid cachexia, is predicted to result from the complex interactions between different cell types involved in the maintenance of skeletal muscle mass, namely, myoblasts, fibroblasts, and macrophages. The complexity within the muscle is further highlighted by the incidence of nonresponsiveness to current RA treatment strategies. Method. This study aimed at determining differences in the cellular responses in a novel human primary cell triple coculture model exposed to serum collected from nonarthritic controls (NC), RA treatment na\u00efve (RATN), and RA treatment-nonresponding (RATNR) patients. Bone morphogenetic protein-7 (BMP-7) was investigated as a treatment option. Results. Plasma analysis indicated that samples were indeed representative of healthy and RA patients\u2014notably, the RATNR patients additionally exhibited dysregulated IL-6\/IL-10 correlations. Coculture exposure to serum from RATNR patients demonstrated increased cellular growth (<jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                        <a:mi>p<\/a:mi>\n                        <a:mo>&lt;<\/a:mo>\n                        <a:mn>0.001<\/a:mn>\n                     <\/a:math>\n                  <\/jats:inline-formula>), while both hepatocyte growth factor (<jats:inline-formula>\n                     <c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                        <c:mi>p<\/c:mi>\n                        <c:mo>&lt;<\/c:mo>\n                        <c:mn>0.01<\/c:mn>\n                     <\/c:math>\n                  <\/jats:inline-formula>) and follistatin (<jats:inline-formula>\n                     <e:math xmlns:e=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\">\n                        <e:mi>p<\/e:mi>\n                        <e:mo>&lt;<\/e:mo>\n                        <e:mn>0.001<\/e:mn>\n                     <\/e:math>\n                  <\/jats:inline-formula>) were reduced when compared to NC. Furthermore, decreased concentration of markers of extracellular matrix formation, transforming growth factor-\u03b2 (TGF-\u03b2; <jats:inline-formula>\n                     <g:math xmlns:g=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\">\n                        <g:mi>p<\/g:mi>\n                        <g:mo>&lt;<\/g:mo>\n                        <g:mn>0.05<\/g:mn>\n                     <\/g:math>\n                  <\/jats:inline-formula>) and fibronectin (<jats:inline-formula>\n                     <i:math xmlns:i=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\">\n                        <i:mi>p<\/i:mi>\n                        <i:mo>&lt;<\/i:mo>\n                        <i:mn>0.001<\/i:mn>\n                     <\/i:math>\n                  <\/jats:inline-formula>), but increased collagen IV (<jats:inline-formula>\n                     <k:math xmlns:k=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M6\">\n                        <k:mi>p<\/k:mi>\n                        <k:mo>&lt;<\/k:mo>\n                        <k:mn>0.01<\/k:mn>\n                     <\/k:math>\n                  <\/jats:inline-formula>) was observed following RATNR serum exposure. Under healthy conditions, BMP-7 exhibited potentially beneficial results in reducing fibrosis-generating TGF-\u03b2 (<jats:inline-formula>\n                     <m:math xmlns:m=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M7\">\n                        <m:mi>p<\/m:mi>\n                        <m:mo>&lt;<\/m:mo>\n                        <m:mn>0.05<\/m:mn>\n                     <\/m:math>\n                  <\/jats:inline-formula>) and fibronectin (<jats:inline-formula>\n                     <o:math xmlns:o=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M8\">\n                        <o:mi>p<\/o:mi>\n                        <o:mo>&lt;<\/o:mo>\n                        <o:mn>0.05<\/o:mn>\n                     <\/o:math>\n                  <\/jats:inline-formula>). BMP-7 further exhibited protective potential in the RA groups through reversing the aberrant tendencies observed especially in the RATNR serum-exposed group. Conclusion. Exposure of the triple coculture to RATN and RATNR serum resulted in dysregulated myoblast proliferation and growth, and ECM impairment, which was reversed by BMP-7 treatment.<\/jats:p>","DOI":"10.1155\/2022\/1524913","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T19:35:14Z","timestamp":1654198514000},"page":"1-14","source":"Crossref","is-referenced-by-count":2,"title":["Therapeutic Benefit in Rheumatoid Cachexia Illustrated Using a Novel Primary Human Triple Cell Coculture Model"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1512-6082","authenticated-orcid":true,"given":"Tracey","family":"Ollewagen","sequence":"first","affiliation":[{"name":"Dept Physiological Sciences, Science Faculty, Stellenbosch University, Stellenbosch, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gareth S.","family":"Tarr","sequence":"additional","affiliation":[{"name":"Winelands Rheumatology Centre, Stellenbosch, South Africa"},{"name":"Dept of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4501-2120","authenticated-orcid":true,"given":"Kathryn H.","family":"Myburgh","sequence":"additional","affiliation":[{"name":"Dept Physiological Sciences, Science Faculty, Stellenbosch University, Stellenbosch, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4672-1412","authenticated-orcid":true,"given":"Helmuth","family":"Reuter","sequence":"additional","affiliation":[{"name":"Winelands Rheumatology Centre, Stellenbosch, South Africa"},{"name":"Dept of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5924-9204","authenticated-orcid":true,"given":"Carine","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Dept of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12320"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1249\/mss.0b013e3181e304c3"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-021-00714-w"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22127"},{"volume-title":"Satellite Cells in Human Skeletal Muscle: Molecular Identification, Quantification and Function","year":"2009","author":"M. 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