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Figure 5 | Arthritis Research & Therapy

Figure 5

From: Elevated extracellular matrix production and degradation upon bone morphogenetic protein-2 (BMP-2) stimulation point toward a role for BMP-2 in cartilage repair and remodeling

Figure 5

Role for bone morphogenetic protein (BMP) during natural reparative response to cartilage damage. To test whether the newly synthesized gremlin adenovirus was efficient in blocking BMP, 3T3 cells were transfected with Ad-gremlin or a control virus and the 28-hour supernatant was incubated with a variety of known concentrations of BMP-2 protein and the BRE-luciferase cell line. This cell line contains a luciferase construct coupled to a BMP-responsive element. Luminescence was measured and showed that Ad-gremlin blocked BMP-2 efficiently. (a) Mice were injected intra-articularly with interleukin-1 (IL-1)-beta to induce cartilage damage. After 2 days, an adenovirus expressing BMP-2, BMP-2 + gremlin, or a control virus was injected. After 4 days, patellae were isolated and incubated in medium with 35SO42- to assess proteoglycan (PG) synthesis (b), or whole knee joints were isolated to measure PG content of the cartilage (c). This showed that BMP-2 boosts PG synthesis and that blocking of BMP activity results in an abrogation of the natural reparative response after cartilage damage. (b) Moreover, blocking of BMP activity with gremlin resulted in an overall outcome of PG depletion. (c) Ad-gremlin injection alone, without IL-1, has no effect (data not shown). Statistical analysis with a Student t test. *p < 0.05; **p < 0.005; ***p < 0.0005. Bre-luc, bone morphogenetic protein-responsive element-luciferase.

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