{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:43:56Z","timestamp":1792622636268,"version":"4.5.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,1,25]]},"abstract":"<jats:p>With an aging population, skeletal fractures are increasing in incidence, including the typical closed and the less common open fractures in normal bone, as well as fragility fractures in patients with osteoporosis. For the older age group, there is an urgent unmet need to induce predictable bone formation as well as improve implant fixation in situations such as hip joint replacement. Using a murine model of slow-healing fractures, we have previously shown that coverage of the fracture with muscle accelerated fracture healing and increased union strength. Here, we show that cells from muscle harvested after 3 d of exposure to an adjacent fracture differentiate into osteoblasts and form bone nodules in vitro. The osteogenic potential of these cells exceeds that of adipose and skin-derived stromal cells and is equivalent to bone marrow stromal cells. Supernatants from human fractured tibial bone fragments promote osteogenesis and migration of muscle-derived stromal cells (MDSC) in vitro. The main factor responsible for this is TNF-\u03b1, which promotes first MDSC migration, then osteogenic differentiation at low concentrations. However, TNF-\u03b1 is inhibitory at high concentrations. In our murine model, addition of TNF-\u03b1 at 1 ng\/mL at the fracture site accelerated healing. These data indicate that manipulating the local inflammatory environment to recruit, then differentiate adjacent MDSC, may be a simple yet effective way to enhance bone formation and accelerate fracture repair. Our findings are based on a combination of human specimens and an in vivo murine model and may, therefore, translate to clinical care.<\/jats:p>","DOI":"10.1073\/pnas.1018501108","type":"journal-article","created":{"date-parts":[[2011,1,5]],"date-time":"2011-01-05T22:50:04Z","timestamp":1294267804000},"page":"1585-1590","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":350,"title":["TNF-\u03b1 promotes fracture repair by augmenting the recruitment and differentiation of muscle-derived stromal cells"],"prefix":"10.1073","volume":"108","author":[{"given":"Graeme E.","family":"Glass","sequence":"first","affiliation":[{"name":"The Kennedy Institute of Rheumatology, Imperial College, Hammersmith, London W6 8LH, United Kingdom; and"},{"name":"Department of Plastic and Reconstructive Surgery, Charing Cross Hospital, Imperial College Healthcare National Health Service Trust, Hammersmith, London W6 8RF, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James K.","family":"Chan","sequence":"additional","affiliation":[{"name":"The Kennedy Institute of Rheumatology, Imperial College, Hammersmith, London W6 8LH, United Kingdom; and"},{"name":"Department of Plastic and Reconstructive Surgery, Charing Cross Hospital, Imperial College Healthcare National Health Service Trust, Hammersmith, London W6 8RF, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Freidin","sequence":"additional","affiliation":[{"name":"The Kennedy Institute of Rheumatology, Imperial College, Hammersmith, London W6 8LH, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Feldmann","sequence":"additional","affiliation":[{"name":"The Kennedy Institute of Rheumatology, Imperial College, Hammersmith, London W6 8LH, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole J.","family":"Horwood","sequence":"additional","affiliation":[{"name":"The Kennedy Institute of Rheumatology, Imperial College, Hammersmith, London W6 8LH, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagdeep","family":"Nanchahal","sequence":"additional","affiliation":[{"name":"The Kennedy Institute of Rheumatology, Imperial College, Hammersmith, London W6 8LH, United Kingdom; and"},{"name":"Department of Plastic and Reconstructive Surgery, Charing Cross Hospital, Imperial College Healthcare National Health Service Trust, Hammersmith, London W6 8RF, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,1,5]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012604"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2006.04.020"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ta.0000195985.56153.68"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-200309000-00006"},{"key":"e_1_3_3_5_2","doi-asserted-by":"crossref","first-page":"S151","DOI":"10.2106\/00004623-200100002-00010","article-title":"Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions","volume":"83","author":"Friedlaender GE","year":"2001","unstructured":"GE Friedlaender, et al., Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. 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