Regulation of immature cartilage growth by IGF-I, TGF-β1, BMP-7, and PDGF-AB: role of metabolic balance between fixed charge and collagen network

Abstract

Cartilage growth may involve alterations in the balance between the swelling tendency of proteoglycans and the restraining function of the collagen network. Growth factors, including IGF-I, TGF-beta1, BMP-7, and PDGF-AB, regulate chondrocyte metabolism and, consequently, may regulate cartilage growth. Immature bovine articular cartilage explants from the superficial and middle zones were incubated for 13 days in basal medium or medium supplemented with serum, IGF-I, TGF-beta1, BMP-7, or PDGF-AB. Variations in tissue size, accumulation of proteoglycan and collagen, and tensile properties were assessed. The inclusion of serum, IGF-I, or BMP-7 resulted in expansive tissue growth, stimulation of proteoglycan deposition but not of collagen, and a diminution of tensile integrity. The regulation of cartilage metabolism by TGF-beta1 resulted in tissue homeostasis, with maintenance of size, composition, and function. Incubation in basal medium or with PDGF-AB resulted in small volumetric and compositional changes, but a marked decrease in tensile integrity. These results demonstrate that the phenotype of cartilage growth, and the associated balance between proteoglycan content and integrity of the collagen network, is regulated differentially by certain growth factors.

Bioengineering Cartilage Growth, Maturation, and Form

“…It has been hypothesized that changes in cartilage size and in maturation (as quantified by the tensile properties) could result by altering the balance of proteoglycan and collagen metabolism (27,41,42). Culturing immature cartilage explants with fetal bovine serum (FBS), insulin-like growth factors-1, or bone morphogenetic protein-7 (BMP-7) resulted in an expansive growth phenotype characterized by large increases in size, stimulation of proteoglycan in excess of collagen, and decreases in tensile stiffness and strength (42). Alternatively, culture with TGF-␤1 promoted cartilage homeostasis with little change in size, composition, or mechanical properties (42).…”

“…Culturing immature cartilage explants with fetal bovine serum (FBS), insulin-like growth factors-1, or bone morphogenetic protein-7 (BMP-7) resulted in an expansive growth phenotype characterized by large increases in size, stimulation of proteoglycan in excess of collagen, and decreases in tensile stiffness and strength (42). Alternatively, culture with TGF-␤1 promoted cartilage homeostasis with little change in size, composition, or mechanical properties (42). The identification of biochemical stimuli which promote maturation in immature cartilage explants has been elusive, though depletion of proteoglycans by chondroitinase-ABC treatment before culture resulted in increased tensile stiffness (27).…”

Memory Encoded Throughout Our Bodies: Molecular and Cellular Basis of Tissue Regeneration

“…There is also a steady increase in the amount of collagenase and other enzymes that are responsible for collagen degradation. Specifically designed compositions of the ECM are critical in the bioengineering of multiple tissues and organs, including bone and cartilage (71)(72)(73)(74), cleft palate repair (4,75), brain injury repair (76), heart valves (77,78), and the skin, which is the most advanced living artificial organ at the present time (42). The elastic component of the ECM, characterized by molecules of elastin that crosslink with one another, confers a resilience to recoil after stretching.…”

Prediction of Articular Cartilage Remodeling During Dynamic Compression with a Finite Element Model

“…AC from the patellofemoral groove has demonstrated consistent GAG and COL densities in previous stud-ies [13,14,17,18]. Biochemical data from [14] was used as it is the most recent and most closely matches the sites harvested from for this study.…”

“…Growth factors such as insulin-like growth factor 1 (IGF-1) and transforming growth factor beta 1 (TGF-β1) have been used to promote geometric growth or alter the constituent balance [13,14,[17][18][19]. Mechanical stimuli such as relative interstitial fluid velocity and mechanical cues such as maximum principle strain direction have been correlated with AC remodeling [20][21][22][23].…”