Bone Morphogenetic Protein (BMP) Localization in Developing Human and Rat Growth Plate, Metaphysis, Epiphysis, and Articular Cartilage

Abstract

We assessed the distribution and relative staining intensity of bone morphogenetic protein (BMP)-1–7 by immunohistochemistry in tibial growth plates, epiphyses, metaphyses, and articular cartilage in one 21-week and one 22-week human fetus and in five 10-week-old Sprague–Dawley rats. In the rats, articular cartilage was also examined. BMP proteins were mostly cytoplasmic, with negligible matrix staining. Highest BMP levels were seen in (a) hypertrophic and calcifying zone chondrocytes of growth plate (BMP-1–7), (b) osteoblasts and/or osteoprogenitor fibroblasts and vascular cells of the metaphyseal cortex and medulla (BMP-1–6), (c) osteoclasts of the metaphysis and epiphysis (BMP-1,-4,-5, and −6), and (d) mid to deep zone articular chondrocytes of weanling rats (BMP-1–7). BMP staining in osteoclasts, an unexpected finding, was consistently strong with BMP-4, −5, and −6 but was variable and dependent on osteoclast location with BMP-2,-3, and −7. BMP-1–7 were moderately to intensely stained in vascular canals of human fetal epiphyseal cartilage by endothelial cells and pericytes. BMP-1,-3,-5,-6, and −7 were localized in hypertrophic chondrocytes adjacent to cartilage canals. We conclude that BMP expression is associated with maturing chondrocytes of growth plate and articular cartilage, and may play a role in chondrocyte differentiation and/or apoptosis. BMP appears to be expressed by osteoclasts and might be involved in the intercellular “cross-talk” between osteoclasts and neighboring osteoprogenitor cells at sites of bone remodeling.