This study was aimed to explore the role of miR-29b-3p and PGRN in chondrocyte apoptosis and the initiation and progress of osteoarthritis (OA). Both miR-29b-3p and PGRN were up-regulated in cartilage tissue from patients with OA. Transfection of miR-29b-3p mimic into rat primary chondrocytes and SW1353 chondrosarcoma cells significantly suppressed PGRN expression and release, induced apoptosis, inhibited proliferation and scratch wound closure. By contrast, transfection of miR-29b-3p inhibitor exhibited the opposite effects. Moreover, the expression and secretion of cartilaginous degeneration-related molecules were also altered by miR-29b-3p. Luciferase reporter gene assay showed rat GRN mRNA is directly targeted and repressed by miR-29b-3p. The fact that recombinant PGRN or shPGRN-mediated PGRN interference abolished miR-29b-3p mimic-induced cell apoptosis and growth inhibition suggested miR-29b-3p affect the cellular functions of chondrocyte through regulating PGRN expression. In vivo, joint cavity injection of miR-29b-3p antagomir prior to surgical induction of OA significantly suppressed the upregulation of miR-29b-3p, whereas further promoted the increased expression of PGRN. Articular chondrocytes apoptosis and cartilage loss in the knee joint of surgically induced OA rats were also ameliorated by the injection of miR-29b-3p antagomir, demonstrated by TUNEL and safranin O-fast green staining. This work showed miR-29b-3p facilitates chondrocyte apoptosis and OA by targeting PGRN, and miR-29b-3p or PGRN may be the potential target for OA treatments.