Abstract
The function of connective tissues depends on the physical and biochemical properties of their extracellular matrix (ECM), which are in turn dictated by ECM protein composition. With the primary objective of obtaining quantitative estimates for absolute and relative amounts of ECM proteins, we performed a systematic review of papers reporting protein composition of human connective tissues. Articles were included in meta-analysis if they contained absolute or relative quantification of proteins found in the ECM of human bone, adipose tissue, tendon, ligament, cartilage and skeletal muscle. We generated absolute quantitative estimates for collagen in articular cartilage, intervertebral disk (IVD), skeletal muscle, tendon, and adipose tissue. In addition, sulfated glycosaminoglycans were quantified in articular cartilage, tendon and skeletal muscle; total proteoglycans in IVD and articular cartilage, fibronectin in tendon, ligament and articular cartilage, and elastin in tendon and IVD cartilage. We identified significant increases in collagen content in the annulus fibrosus of degenerating IVD and osteoarthritic articular cartilage, and in elastin content in degenerating disc. In contrast, collagen content was decreased in the scoliotic IVD. Finally, we built quantitative whole-tissue component breakdowns. Quantitative estimates improve our understanding of composition of human connective tissues, providing insights into their function in physiology and pathology.
Highlights
The extracellular matrix (ECM) is a composite of cell-secreted molecules that offers biochemical and structural support to cells, tissues, and organs[1]
A great deal of variance exists around reported incidence rates of disc degeneration, some reports suggest a rate as high as 70% in some populations, and the disorder is usually thought to be linked to back pain[14,15]
12 reported the absolute quantitative information for proteins derived from articular cartilage21–32; 9 for intervertebral discs (IVD)16,33–40; 3 each for tendon[41,42,43] and skeletal muscle44–46; 2 for ligament[41,42]; and 1 for adipose tissue (Fig. 1b)[47]
Summary
The ECM is a composite of cell-secreted molecules that offers biochemical and structural support to cells, tissues, and organs[1]. The structural requirements determine the mechanical properties of the ECM, which depend on the protein composition of the matrix, the abundance of collagen and elastin[1]. Ligaments, adipose tissue, bone, cartilage, and intervertebral disc (IVD) are connective tissues involved in diverse physiological roles including nutrient storage, endocrine function, and providing structural integrity[8,9,10]. This is well studied for disorders that affect cartilage, such as osteoarthritis, and IVD degeneration. Osteoarthritis (OA), a common disorder occurring in 60% of adults over the age of 65 in Europe and North America, leads to pathological changes in the structure and composition of the cartilage matrix, which www.nature.com/scientificreports/. We set two additional secondary objectives: 1) to quantify the changes in ECM composition in distinct pathologies; 2) to combine the outcomes for ECM proteins with reference values for other components to build quantitative estimates of whole tissue composition
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