Work

Invited Perspective: New Insight into Cadmium-Related Osteoporosis Yields Hope for Prevention and Therapy

Year: 2024

Type: article

Abstract: In this issue of Environmental Health Perspectives, Liu et al. present a mechanistic mouse study on cadmium (Cd)-induced osteoporosis and propose a hypothesis that nuclear factor erythroid 2-related factor 2 (NRF2) and its Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family member nuclear factor erythroid 2-related factor 1 (NRF1) coordinate osteoclastogenesis during Cd exposure. 1 This study offered new insights into cadmium-related osteoporosis, providing hope for both prevention and therapy.With an increasing life expectancy globally, we can expect an increased number of people with age-related bone loss and osteoporosis.2 The causative or risk factors for osteoporosis include genetic factors, endocrine, gastrointestinal, rheumatic and autoimmune diseases, lifestyle change, and environmental factors.3 Chronic exposure to Cd is associated with osteoporosis, even though there are sex and racial differences for the associated levels between Cd exposure and osteoporosis.[4][5][6] However, the specific mechanisms driving this association remain incompletely understood, and Liu et al. have provided an innovative and important insight.Many metals induce an increase in reactive oxygen species (ROS) via mitochondria-dependent and -independent mechanisms, resulting in oxidative damage.7,8 Nrf1 and Nrf2 are the two master transcription factors regulating antioxidant defense, [9][10][11] including its response to metal challenge.Emerging evidence indicates the protection of Nrf2-mediated antioxidant pathways against metalinduced oxidative damage.Beyond this protection against oxidative damage, as a nuclear transcriptional factor Nrf2 also acts directly and indirectly by modulating a wide range of cell fates, including cell metabolism, proteasome activity, and cell differentiation.[9][10][11] The insight gleaned by Liu et al. is their finding of the cross-regulation between Nrf1 and Nrf2 in osteoclastogenesis in response to Cd exposure, 1 as outlined in Figure 1.Nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1 (NFATc1) signaling plays an essential role in osteoporosis by increasing a number of osteoclast-specific genes, such as tartrate-resistant acid phosphatase (TRAP), cathepsin K, calcitonin receptor, and osteoclast-associated receptor.12 Reportedly, human

Source: Environmental Health Perspectives

DOI: 10.1289/ehp15263

Author: Lu Cai

Institution: University of Louisville

Language: English

Topic: Heavy Metal Exposure and Toxicity

Subfield: Health, Toxicology and Mutagenesis

Field: Environmental Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,500