Genetic Factors in Bone Growth and Skeletal Disorders

Genetic Influence on Skeleton

• Skeleton shape, size, and construction are determined by genetic plans.
• Genetic changes affecting bone growth can lead to skeletal changes.
• Numerous skeletal disorders have genetic roots (e.g., brittle bones, bowed bones, shortened limbs).

Achondroplasia

• Most common genetic skeletal disorder.
• Occurrence: 1 in 25,000 live births.
• Affects nearly all bones, especially noticeable in limbs.
• Results in individuals being approximately 25% shorter than average height.

Bone Growth Mechanisms

• Two primary processes of bone formation.
• Achondroplasia affects endochondral bone growth (lengthening bones via cartilage growth plates).

Cartilage Growth Plates

• Special cartilage in these plates is replaced by bone.
• Disruption leads to abnormalities in bone length and shape.
• Growth plates exist throughout the body, affecting bone growth globally.

Growth Plate Structure

• Comprised of layers of cartilage cells.
• Cells divide, grow, mature, and are replaced by bone cells.
• New bone layers form at the growth plate's edge, akin to brick layering.

Regulation of Bone Growth

• Regulated by numerous signals, mainly small molecules in the body.
• Cells have receptors to interpret signals.
• Receptors are essential for bone growth regulation.

FGFR3 and Achondroplasia

• FGFR3 receptor gene alteration in achondroplasia.
• FGFR3 normally interacts with FGF molecules to regulate growth.
• In achondroplasia, FGFR3 is constantly active without FGF, inhibiting growth.

FGFR3 Receptor Function

• Consists of external and internal parts.
• Activated by fibroblast growth factors (FGFs) in normal conditions.
• In achondroplasia, it is active without FGFs, constantly signaling to stop bone growth.

Other Growth Control Components

• NPRB receptor works with CNP molecule to promote growth.
• CNP presence turns off FGFR3's stop signal, allowing growth.
• Normally, this balances FGFR3 and CNP-NPRB pathways to fine-tune growth.

Implications for Treatment

• FGFR3 signals stronger in achondroplasia, overpowering CNP signals.
• CNP system offers potential for therapeutic intervention to balance pathways.

Conclusion

• Understanding genetic impact on skeleton development is crucial.
• Scientific progress in this area could lead to better understanding and treatment of bone growth disorders.