Good versus bad fibroblasts

Are fibroblasts good or are they bad?

We need to talk about the good and the bad fibroblasts – the dangerous fibroblasts that overgrow organs and destroy organ function, but also the necessary specialized fibroblasts in bone, the osteoblasts. 

Fibroblasts are an important type of cell in the human body that play a crucial role in tissue repair and maintenance. However, not all fibroblasts are created equal – there are both good and bad fibroblasts that have vastly different effects on the body.

The dangerous fibroblasts, known as myofibroblasts, are responsible for pathological tissue remodeling in various diseases, such as fibrosis. These fibroblasts overgrow organs and destroy organ function. While myofibroblasts play a role in wound healing, their persistence and unchecked growth can lead to excessive scarring and tissue damage.

Pathological bone remodeling phenotypes

On the other hand, there are specialized fibroblasts, such as osteoblasts, that are necessary for maintaining bone health. Osteoblasts are responsible for producing the extracellular matrix that makes up bone tissue, and are crucial in the process of bone formation.

Unfortunately, the success in biomedical sciences such as genomics and proteomics is not paralleled in the medical product development methods, resulting in a lack of translation into improved drug safety and efficacy. This can lead to some antifibrotic treatments having deleterious effects on bone fibroblasts, such as osteoblasts, and may cause unwanted side effects.

Proposed phenotypes of endochondral bone formation in rheumatic diseases

In rheumatic diseases, bone inflammation and remodeling phenotypes are proposed to be a result of endochondral bone formation. Studies have identified bone as a possible endocrine organ, and the availability of valid biochemical bone markers suggests that assessing bone turnover should also play an important role in general safety pharmacology.

To address this issue, there is a need for improved methods to assess the effects of treatments on different types of fibroblasts. This is where bone inflammation panels come in – these panels can be used to assess whether a treatment is having a deleterious effect on bone fibroblasts, such as osteoblasts.

In conclusion, while fibroblasts play a crucial role in tissue repair and maintenance, it is important to distinguish between the good and bad fibroblasts. Unchecked growth of myofibroblasts can lead to tissue damage and organ dysfunction, while osteoblasts are necessary for maintaining bone health. Improved methods of assessing the effects of treatments on different types of fibroblasts, such as bone inflammation panels, can help ensure that treatments are safe and effective.

With our bone inflammation panel, you can assess whether your treatment is having a deleterious effect.

Related publications:

Should biochemical markers of bone turnover be considered standard practice for safety pharmacology?

Biochemical markers in osteoarthritis with lessons learned from osteoporosis

Role of biochemical markers in the management of osteoporosis

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    The effect of copper depletion therapy on breast cancer patients

    The affect on the collagen microenvironment in breast cancer patients

    In a recently published study based on a collaboration between Nordic Bioscience, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, and Nancy E. and Peter C. Meinig School of Biomedical Engineering, we have examined the effect of copper depletion therapy on the collagen microenvironment in breast cancer patients with a high risk of relapse.

    Tetrathiomolybdate (TM) is a novel, copper-depleting compound associated with promising survival in a phase II study of patients with high-risk and triple-negative breast cancer. In the study, levels of all collagen biomarkers were higher in those with the disease, metastatic and adjuvant, as compared with healthy controls. 

    Baseline biomarkers of collagen crosslinking (LOXL2), collagen formation (PRO-C3), and collagen degradation (C1M and C6M) in the exploratory cohort

    We propose a novel mechanism for preventing metastases through altered collagen processing in the tumor microenvironment. We hypothesize that decreased collagen cross-linking and increased degradation caused by the treatment may alter the immune response in the pre-metastatic sites and thereby decrease the metastatic potential.

    The effect of copper depletion therapy on collagen turnover in breast cancer patients

    Preclinical studies revealed decreased collagen deposition, lower levels of myeloid-derived suppressor cells, and higher CD4+ T-cell infiltration in TM-treated mice compared with controls.

    In conclusion, the study showed novel mechanisms of TM targeting the TME and immune response with potential applications across cancer types.

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