Changes in the orientation of proteoglycans during the early development of natural murine osteoarthritis

At least 80% of male STR/ORT mice naturally develop osteoarthritis that predominantly affects the medial tibial cartilage. Overt osteoarthritic changes, as judged by radiological and histological abnormalities, become apparent after 30 weeks of age. Consequently, mice < 30 weeks of age were used to investigate early changes in the cartilage matrix related to the natural development of osteoarthritis, without the need for experimental intervention to induce this condition. Quantitative Alcian blue staining showed little change in the total amount of proteoglycans in mice of this age. Polarized light microscopy of the birefringence induced by such staining demonstrated a progressive decline in the orientation of the proteoglycans in the medial cartilage of these mice. This decline was not found in CBA mice, which only very rarely develop osteoarthritis of this joint. Such progressive disorganization of the proteoglycans would be likely to permit the increased free water‐content characteristic of osteoarthritic cartilage.