Regulation of Joint Tissues and Joint Function: Is There Potential for Lessons to Be Learned Regarding Regulatory Control from Joint Hypermobility Syndromes?

Normal development of joints starts in utero with the establishment of a cellular and extracellular matrix template. Following birth, individual joint tissues grow and mature in response to biochemical and mechanical signals, leading to a coordinated pattern of further maturation resulting in a joint that functions as an organ system. Each joint develops and matures as an organ system defined by the biomechanical environment in which it will function. For those with joint hypermobility syndromes, either defined by specific genetic mutations or not (i.e., Ehlers-Danlos syndrome, Marfan syndrome, Loey-Dietz syndrome, hypermobility-type Ehlers-Danlos syndrome), this process is partially compromised, but many aspects of joint tissue maturation and resulting joint function is retained such that the organs form and retain partial function, but it is compromised. Comparing the characteristics of what is known regarding development, growth, maturation, and response to stressors such as puberty, pregnancy, and aging in joints of those without and with joint hypermobility leads to the conclusion that in those that have hypermobility syndromes, the joint systems may be compromised via a failure to undergo mechanical maturation, possibly via defective mechanotransduction. Given the breadth of the mutations involved in such hypermobility syndromes, further characterization of this concept may reveal commonalities in their impact on tissue maturation, which will further inform regulatory aspects of normal tissue and functional integrity. This review/perspective piece will attempt to detail such comparisons and summarize how further study will aid in further understanding.