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FAM98 Family Proteins Play Distinct Roles in Osteoclastogenesis and Bone Resorption.

Lei Wang1, Tarun Minocha2, Bhaba K Das2

  • 1Department of Orthopedics, The Third People's Hospital of Hefei, Third Clinical College, Anhui Medical University, Hefei 230032, China.

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|January 25, 2025
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Summary

The three FAM98 proteins (FAM98A/B/C) have distinct roles in osteoclast function. Fam98b and Fam98c impact osteoclastogenesis and lysosome trafficking, while Fam98a

Keywords:
Fam98aFam98bFam98cPlekhm1bone resorptionlysosomeosteoclast

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Area of Science:

  • Cell Biology
  • Bone Biology
  • Molecular Biology

Background:

  • The physiological functions of the three FAM98 family proteins (FAM98A/B/C) are largely unknown.
  • Previous research indicated Fam98a's role in murine osteoclast lysosome trafficking and bone resorption.

Purpose of the Study:

  • To investigate the distinct roles of FAM98A, FAM98B, and FAM98C in osteoclastogenesis and function.
  • To elucidate the specific contributions of each FAM98 family member to osteoclast biology.

Main Methods:

  • Gene expression analysis of Fam98 genes in osteoclast precursors and mature osteoclasts.
  • Short-hairpin RNA (shRNA)-mediated knockdown of Fam98b and Fam98c in osteoclast precursors.
  • Phenotypic analysis of osteoclastogenesis, lysosome trafficking, and bone resorption in Fam98-depleted osteoclasts.
  • Assessment of bone mass in Fam98a-null mice.

Main Results:

  • All three Fam98 genes (FAM98A/B/C) are expressed in osteoclasts.
  • Fam98c knockdown attenuated osteoclastogenesis.
  • Fam98b depletion disrupted osteoclast lysosome trafficking and bone resorption, similar to Fam98a.
  • Fam98a deficiency did not affect bone mass in mice, potentially due to Fam98b compensation.

Conclusions:

  • The three FAM98 proteins play distinct roles in osteoclastogenesis and osteoclast function.
  • Further investigation is needed to fully understand the specific functions of each FAM98 protein.
  • Fam98b and Fam98c are crucial for osteoclast function, while Fam98a's role may be compensated by Fam98b.