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The number of chondrocyte cells created and their maturation process can be influenced by multiple different genes and proteins. Two proteins, bone morphogenetic protein 4(BMP-4) and fibroblast growth factor 2(FGF2) have been seen to influence the amount of differentiation into chondrocytes. [4]
The expression of Sox9 induces the expression of BMP, which causes chondrocytes to proliferate and differentiate. [7] L-Sox5 and Sox6 share this common role with Sox9. L-Sox5 and Sox6 are thought to induce the activation of the Col2a1 and the Col11a2 genes, and to repress the expression of Cbfa1, a marker for late stage Chondrocytes.
The COL2A1 gene is located on the long (q) arm of chromosome 12 between positions 13.11 and 13.2, from base pair 46,653,017 to base pair 46,684,527. The expression of COL2A1 is regulated by SOX-9 and retrotransposon gag-like-3 gene RTL3 in chondrocytes. [6]
Collagen alpha-1(X) chain is a protein that in humans is a member of the collagen family encoded by the COL10A1 gene. [5] [6] This gene encodes the alpha chain of type X collagen, a short chain collagen expressed by hypertrophic chondrocytes during endochondral ossification. Unlike type VIII collagen, the other short chain collagen, type X ...
It is encoded by 6 genes: COL6A1, COL6A2, COL6A3, COL6A4, COL6A5, and COL6A6. [3] The chain lengths of α1(VI) and α2(VI) are about 1,000 amino acids. The chain length of α3(VI) is roughly a third larger than those of α1(VI) and α2(VI), and it consists of several spliced variants within the range of 2,500 to 3,100 amino acids.
SOX-9 recognizes the sequence CCTTGAG along with other members of the HMG-box class DNA-binding proteins. It is expressed by proliferating but not hypertrophic chondrocytes that is essential for differentiation of precursor cells into chondrocytes [7] and, with steroidogenic factor 1, regulates transcription of the anti-Müllerian hormone gene.
Genes of the Hh family, Sonic Hedgehog (Shh), Desert Hedgehog (Dhh) and Ihh regulate several fetal developmental processes. [10] The Ihh homolog is involved in the formation of chondrocytes during the development of limbs. [10] The protein is released by small, non-proliferating, mature chondrocytes during endochondral ossification. [10]
TGF-β is important for cell proliferation and differentiation during skeletogenesis. During this process, TGF-β can stimulate differentiation into either chondrocytes or osteoblasts via FGF, Msx1, and Ctgf signalling pathways. General gene knock out of the TGF-β resulted in death.