Targeting post-translational modifications: novel insights into bone metabolic diseases

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Bone metabolic diseases involve abnormal bone mass and metabolism, influenced by oxidative stress and nutritional factors.
• Post-translational modifications (PTMs) are crucial for protein regulation and implicated in bone disease pathogenesis.
• Existing reviews often neglect the complex interplay and cross-talk between various PTMs in bone health.

Purpose of the Study:

• To systematically review diverse PTMs, including phosphorylation, methylation, ubiquitination, glycosylation, and novel modifications like lactylation and sulfhydration.
• To elucidate the mechanisms and interrelationships (cross-talk) among PTMs in regulating bone metabolism.
• To highlight the role of aberrant PTMs in disrupting bone homeostasis and their involvement in diseases such as osteoarthritis, osteoporosis, osteosarcoma, and rheumatoid arthritis.

Main Methods:

• Comprehensive literature review of PTMs in bone metabolic diseases.
• Analysis of regulatory mechanisms and signaling pathways affected by PTMs.
• Synthesis of current knowledge on PTM cross-talk and its impact on bone pathophysiology.

Main Results:

• Detailed overview of 15 distinct PTMs and their specific roles in bone health and disease.
• Identification of key signaling pathways regulated by PTMs, including those involved in cellular dysfunction.
• Evidence for the significant impact of PTM interplays on bone metabolic homeostasis.

Conclusions:

• Aberrant PTMs disrupt bone metabolic homeostasis, contributing to diseases like osteoarthritis and osteoporosis.
• Understanding PTM mechanisms and their cross-talk offers potential for novel therapeutic targets.
• Further research into PTMs provides a foundation for developing more effective treatments for bone metabolic disorders.