Abstract Objective: In these studies,we investigated the timing and location of chondrocyte colony-like clusters in cartilage tissue during the development of human knee osteoarthritis(OA),and explored the biological properties of chondrocytes in colony-like clusters and their significance for degenerative cartilage tissue. Methods: Osteoarthritis Research Society International (OARSI) grade 0~6 cartilage tissue was obtained from the human tibial plateau, and histologicalsections were made to observe whether there were chondrocyte colony-like clusters in the cartilage tissue and where they occurred. Immunohistochemistry, PCR and western blotting were used to detect the biological properties of chondrocytes in the colony-like clusters and to describe the histopathological stages of the colony-like clusters according to the properties of thechondrocytes in the cluster. Results: There were a large number of chondrocyte colony-like clusters in the middle zone of OARSI grade 3 and grade 4 cartilage tissue.The chondrocytes in the colony-like clusters rapidly proliferated from one to a certain number and then rapidly underwent hypertrophic changes,synthesizing and releasing the MMP-13 protein to degrade cartilage tissue and enlarge chondrocyte lacunae.Eventually, the chondrocytes in the colony-like cluster underwent apoptosis and disappeared, leaving large empty chondrocyte lacunae.According to this process, chondrocyte colony-like clusters could be divided into four stages. Conclusions: Chondrocyte colony-like clusters mainly formed during the development of OA of OARSI grades 3 and 4 could cause the cartilage tissue to become looser and more porous, with more severe cartilage degeneration.