Purpose: Reduction of ADL by osteoarthritis of the knee (knee OA) is a major factor threatening healthy life expectancy. Thus, clarification of the pathology of knee OA is desired. We reported that cartilage part of osteophyte could be detected using T2 mapping MRI and medial meniscal extrusion (MME) was associated with medial tibial osteophyte evaluated by T2 mapping MRI in early-stage knee OA (Arthritis Res Ther, 19:201, 2017). However, there is no report showing cartilage part of osteophytes in early stage knee OA in human, histologically. The aim of this study was to investigate the morphological feature of osteophytes in human knee OA using cadavers. Methods: All cadavers were from persons who had donated their bodies for medical education and research to our university. Prior to donation, written consent was obtained from the individuals and families. The protocol for the present research project was approved by the Ethics Committee of our university. Fourteen left legs were collected from embalmed Japanese cadavers (3 males, 11 females; average age, 83.3±8.2 years of age), which were dissected by medical students in the gross anatomy course at Juntendo University School of Medicine. Knee joint was dissected out proximal and distal 10cm from the knee articular surface after skin removal. Anteroposterior view radiographs were taken and then evaluated according to the Kellgren-Lawrence (K/L) classification. Then, the patella and muscle were removed and the 2 cm width of medial parts of the knee joint remaining the medial collateral ligament were collected. They were fixed in 10% neutral buffered formalin, decalcified, and embedded in paraffin. The samples were cut into sections and stained with safranin-O and fast green. The histological features of medial tibial plateau (MTP) was quantified by histological grading scores. The cartilage degradation score used in the present study was the modified Mankin score (0-18) (Mankin, JBJS, 1971). The osteophyte formation score used in the present study was a score for its maturity with 5 degrees (0-4; grade 0: no osteophyte like lesion, grade 1: pre-cartilagious lesion, grade 2: predominantly cartilaginous, grade 3: mixed cartilage and bone, grade 4: predominantly bone), which was modified by the score for the evaluation of osteophyte in mouse model, as previously reported (Kamekura et al., Osteoarthritis Cartilage, 2005). Results: The severities of radiographic knee OA of the subjects in the present study were 7 (50.0%) for K/L grade 1, 5 (37.7%) for K/L grade 2, 2 (14.3%) for K/L grade 4, respectively. The cartilage degradation scores of the subjects were 4.1 [standard deviation (SD): 1.5] for K/L grade 1, 5.2 (1.3) for K/L grade 2, 15.0 (3.0) for K/L grade 4, respectively. Osteophytes were observed in all the samples of the subjects, regardless of the radiographic severity of knee OA. The osteophyte scores of the subjects were 7 (50.0%) for grade 1, 3 (21.4%) for grade 2, 2 (14.3%) for grade 3, and 2 (14.3%) for grade 4, respectively (Fig. 1). The histological sections with grade 4 of osteophytes were consisted of proliferative, pre-hypertrophic, hypertrophic, and ossification zones, while those with grade 1 were consisted of reduplication of synovial tissues. Conclusions: The histological examinations showed that osteophytes were existed in all the samples of the subjects, which showed the radiographic knee OA changes not only with K/L grade 2 to 4 but also with K/L grade 1. The developmental processes of the osteophyte in knee OA in human were similar to those observed in the growth plate in the murine model, which is the process similar to the endochondral ossification.