Fkpb10 Deletion Causes Tendinopathy in Osteogenesis Imperfecta

Mobility issues are common in patients with osteogenesis imperfecta (OI) – especially tendinopathy, or tendonitis. But why does this happen? According to Medical XPress, a study performed by Baylor College of Medicine researchers showed that Fkpb10 gene deletions could be the cause. Take a look at the study findings published in the Proceedings of the National Academy of Sciences (PNAS).

Tendinopathy

According to Healthline:

Tendons are strong, rope-like tissues containing collagen protein [that] connect your muscles to your bones. Tendinopathy, also called tendinosis [or tendonitis], refers to the breakdown of collagen in a tendon, [which]  causes burning pain in addition to reduced flexibility and range of motion.

Although researchers have, in the past, explored the genetic underpinnings of joint deformities in patients with OI, researchers wanted to understand the joint pathologies. Within this study, researchers used mice models of OI. To begin, they deleted Fkpb10 in ligaments and tendons. Next, researchers determined that Fkpb10 deletions caused contracture of the tendon. In contracture, the mice models experienced the shortening and hardening of tendons, ultimately reducing range of motion and causing rigid joints. Additionally, researchers noted other signs of tendinopathy, such as joint inflammation and localized cartilage formation.

Next, researchers tested the mice models. They discovered that the Hedgehog signaling protein had become activated in joints when Fkpb10 was deleted, causing Hedgehog signaling dysregulation. Researchers then treated the mice models with a Hedgehog signaling inhibitor. Through this administration, the researchers determined that this therapy prevented the symptoms associated with tendinopathy and improved joint mobility.

Ultimately, researchers now believe that Hedgehog signaling inhibitors could be effective treatments for patients with tendinopathy, alone or when caused by other conditions (such as OI). However, additional research is needed to determine the veracity of this belief.

Osteogenesis Imperfecta (OI)

Typically, COLA1A1 or COL1A2 gene mutations cause most osteogenesis imperfecta (OI) diagnoses. OI, or brittle bone diseases, consists of a group of rare genetic disorders which affect the bones. Normally, COLA1A1 and COL1A2 direct the body to produce type 1 collagen,  which plays a role in bone and connective tissue formation. Collagen plays a role in connective tissue health, which supports the entire body. In patients with OI, the collagen is abnormal, defective, or just not produced enough. As a result, patients have bones which easily break or fracture, sometimes with no real cause.

There are multiple forms of OI. For example, around 50% of patients have type I, the mildest form, characterized by few fractures or deformities. Alternately, Type II is the most severe form of OI and can be fatal within weeks of birth. Type III is the most severe form in babies who live through infancy. Finally, type IV vacillates between mild and severe symptoms and may be clearest during development. There are an additional four known forms of OI (types V through VIII), although these are considered rarer.

Symptoms depend on which form of OI is present. In Type I, patients may experience bluish discoloration in the whites of the eyes, as well as multiple bone fractures. Next, in type II, patients may be born with fragile skin, fractures, bone malformations, and underdeveloped lungs. For patients with Type III OI, they may experience symptoms from both type I and II. Finally, patients with type IV OI often have fragile bones, scoliosis, a triangular facial appearance, and a short stature.

Other symptoms that may appear include:

  • Muscle weakness
  • Bone deformities, such as bowed legs
  • Easy bruising
  • Hearing loss (in early adulthood)
  • Soft and discolored teeth
  • Difficulty breathing
Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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