Treatment of cartilage with β-aminopropionitrile accelerates subsequent collagen maturation and modulates integrative repair

Integrative repair of cartilage was previously found to depend on collagen synthesis and maturation. β-aminopropionitrile (BAPN) treatment, which irreversibly blocks lysyl oxidase, inhibited the formation of collagen crosslinks, prevented development of adhesive strength, and caused a buildup of GuHCl-extractable collagen crosslink precursors. This buildup of crosslink precursor in the tissue may be useful for enhancing integrative repair. We tested in vitro the hypothesis that pre-treatment of cartilage with BAPN, followed by washout before implantation, could be a useful therapeutic strategy to accelerate subsequent collagen maturation. In individual cartilage disks, collagen processing was reversibly blocked by BAPN treatment (0.1 mM) as indicated by a BAPN-induced increase in the total and proportion of incorporated radiolabel that was extractable by 4 M guanidine-HCl, followed by a decrease, within 3-4 days of BAPN washout, in the proportion of extractable radiolabel to control levels. With a similar pattern, integration between pairs of apposed cartilage blocks was reversibly blocked by BAPN treatment, and followed by an enhancement of integration after BAPN washout. The low and high levels of integration were associated with enrichment in [3H]proline in a form that was susceptible and resistant, respectively, to extraction. With increasing duration up to 7 days after BAPN pre-treatment, the levels of [3H]proline extraction decreased, and the development of adhesive strength increased. Thus, BAPN can be used to modulate integrative cartilage repair.