The present disclosure relates to recombinant viral vectors, to pharmaceutical compositions comprising such recombinant vectors, and to methods for prevention and treatment of osteoarthritis in mammals. In particular, this disclosure provides adeno-associated virus (AAV) vectors capable of expressing, in a host, osteoprotective/chondroprotective bioactive proteins, including hyaluronan synthase 2 (HAS2) and lubricin (PRG4). Methods of production of these AAV are provided, as are methods of treatment of osteoarthritis in mammalian joints, by the long-term gene expression of osteoprotective/chondroprotective proteins, including HAS2 and PRG4, in both synovial and chondrocyte cells.