Quote from SecondLifeGuide on October 6, 2024, 6:46 am

I discuss this in an article on my website: https://secondlifeguide.com/2023/11/04/how-accutane-causes-joint-pain-and-stunted-growth-and-why-lithium-helps/

 

Cartilage 

Cartilage is mostly composed of cells called Chondrocytes, they function by maintaining the extracellular matrix whilst also releasing substances to make the cartilage strong and flexible. They are found in all joints as well as in the intervertebral discs and provide the cushioning in joint movements.

Cartilage begins to grow in early development in a process called chondrification, which is also pivotal in skeletal development since skeletal structures rely upon cartilage for new bone growth. Endochondral ossification is process of skeletal development that using the cartilage as a template. The Chondrocytes transform during this process first by enlarging, before then dying and calcifying. Osteoblasts (bone generating cells) then migrate into this area and lay down a bone matrix. [6]

One of the most fundamental signalling pathways in regulating new bone growth is the Wnt/Beta-catenin signalling pathway. Beta-catenin is a protein that signals for growth in tissues throughout the body, but is particularly important in bone health, determining both osteogenesis (formation of bone) and chondrogenesis. [5]

Beta-catenin is typically bound within a structure called the ‘destruction complex’, constantly breaking it down. It can be released from the destruction complex in response to PI3K/AKT signalling, which is regulated by growth factors such as IGF-1 (the metabolite of Human Growth Hormone). 

 

The role of beta-catenin

Retinoic acid has been shown to significantly alter the differentiation pattern of chondrocytes. This most plainly observed in foetuses overexposed to retinoids, which display craniofacial and limb malformation. In vitro evidence shows that Retinoic acid inhibits the formation of chondroblasts (the cells that form chondrocytes), resulting in the cessation of cartilage formation and ultimately the loss of pre-existing cartilage structures. [7] [8]

Retinoic acid has been shown to exert many of its effects by decreasing beta-catenin, by enhancing its destruction complex action through suppressing the PI3K-Akt pathway.[9][10]Many of the observed effects of retinoic acid on chondrocytes match the known effects of suppressing beta-catenin signalling on chondrocytes, suggesting that this may be the relevant mechanism of action. Inhibition of beta-catenin in chondrocytes resulted in increased cell apoptosis (cell death) and “articular cartilage destruction”. [11]

The role of beta-catenin in development of bone and cartilage is complex, and the direction of effect depends on the state of maturation of the tissue. Early in development, beta-catenin inhibits the differentiation of mesenchymal stem cells into cartilage, and conversely the effect is enhanced by Retinoic acid. [12] The nature of the spatiotemporal patterning is guided by HOX genes and the different RAR isoforms.[13]

The potentially destructive effects of Accutane on cartilage structures could be of particular concern for patients treated during their key growing years. By inhibiting new cartilage growth Accutane could prematurely seal the epiphyseal growth plates at the end of long bones. It’s hard to say exactly how profound this effect could be, however one case study posits that an individual missed their projected growth target by 5cm! [14][21]