BMP-2 shows characteristic extracellular patterns in osteoarthritic cartilage: a preliminary report

To determine bone morphogenetic protein (BMP)-2 protein and Aggrecan in osteoarthritic and healthy cartilage with special regard to localization and degree of cartilage damage 95 samples representing osteoarthritic cartilage and 17 samples out of normal cartilage were graded histological by Mankin Score and were studied by immunohistochemistry for the expression of BMP-2 and Aggrecan. BMP-2 protein was detected intracellular in normal and in osteoarthritic cartilage. Extracellular BMP-2 was detected exclusively in osteoarthritic cartilage and exhibits characteristic extracellular patterns: samples with BMP-2 in the extracellular matrix show BMP-2 negative coronae around BMP-2 positive cells. There is a statistically significant increase in the prevalence of extracellular BMP-2 with increasing ICRS grade/Mankin grade. Aggrecan was detected in the extracellular matrix und exhibited coronas throughout all layers. A decline of extracellular Aggrecan with increasing ICRS grade could be observed. Normal cartilage shows no intracellular Aggrecan whereas an increase in the prevalence of intracellular Aggrecan could be detected in osteoarthritic cartilage. The appearance of intracellular Aggrecan is often associated with extracellular BMP-2. The detection of BMP-2 protein in normal as well as in osteoarthritic cartilage highlights the importance of BMP-2 in tissue homeostasis and point to a putative role for maintaining tissue integrity during the development of osteoarthritis. The co-appearance of extracellular BMP-2 and intracellular Aggrecan indicates a functional relationship. The most interesting result is the characteristic distribution of extracellular BMP-2. These coronas seem to have an impact during progression of osteoarthritis and need to be further investigated.