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For example, intradiscal injection of bone morphogenetic protein-2 (BMP-2) induced degenerative changes [92] and weekly intradiscal treatment with growth and differentiation factor-5 (GDF-5) or insulin-like growth factor-1 (IGF-1) resulted in inflammatory reactions in the adjacent vertebrae and connective tissue infiltrates in the NP, causing the IVD to collapse [93]