Mast Cell Activation and Osteoporosis

In this vlog with Betty Murray, PhD-C, MS, CN, IFMCP, she discusses what mast cells are; how they become activated; and, how mast cells may be playing a role in your bone metabolism and bone turnover.

 

Want to listen in to the episode? Hit the “play” button below:

 

 

Transcript

Mast Cell Activation & Osteoporosis

[00:00:00] Welcome to the BoneCoach Mast Cell, Histamine, and Osteoporosis Vlog and Blog. This is Betty Murray. I’m a PhD candidate and a certified nutritionist and certified functional medicine practitioner through the Institute of Functional Medicine. And I’m going to talk a little bit today about histamine mast cells and their role in osteoporosis.

[00:00:28] So let’s get to it. For many of you, you may be wondering what the heck is a mast cell. Mast cells are important cells of the immune system that are involved in many physiological and pathological conditions, including things like bone metabolism and bone disorders. Mast cells are located in the bone marrow and they secrete a wide spectrum of mediators.

[00:00:52] Think of these as little messengers, which can be rapidly released upon activation. Once the mast cell has become mature. And then it can act on different tissues, like your mucosal barriers or your connective tissues. So said another way, mast cells are part of your immune system response that are first responders to incoming pathogens.

[00:01:14] So for instance, if you have allergies and you step outside and you get exposed to pollen, you get a histamine response, which is part of the mast cell activation that is trying to remove that pathogen as seen as the pollen itself, from your system to try and get it off the mucosal barriers. So mast cells mediate a significant portion of our immune response, but mast cells also act on different tissues in different ways.

[00:01:43] So what’s interesting is when we’ve looked in studies at mast cells, what they’ve started to see is that the molecules the mast cells use to communicate (things like histamine and or other inflammatory things like Interleukin-6), actually exert control and activity over the osteo-catabolic activity at the bone.

[00:02:06] In other words, the breakdown activity of the bone by promoting osteoclast formation…and they can also inhibit osteoblast activities. So mast cells could potentially act in both a negative way by increasing bone breakdown, but in some ways, they may be able to be osteo-protective by stimulating osteoblasts and by reducing osteoclast growth.

[00:02:33] So all that to say, there’s a lot of opportunity for research to continue in mast cells and histamine. So let’s talk a little bit more about what that means. Mast cells may contribute to the pathogenesis of primary and secondary osteoporosis and other inflammatory conditions and inflammatory diseases like rheumatoid arthritis and osteoarthritis. Because there’s increasing numbers of mast cells found in patients

[00:03:03] suffering from these diseases, we know that they may play a role specifically in the actual pathogenesis of those diseases. Mast cells also regulate bone healing after fracture by influencing the inflammatory response toward the fracture itself…mast cells help what they call revascularization, which means your body reproducing or producing more blood vessels to increase blood flow, bone formation,

[00:03:30] and calcification. Those are all remodeling processes controlled by osteoclasts. So let’s look a little deeper in what’s really happening. So mast cells are actually in the tissue. So they actually act in the tissues and they’re best known for promoting allergic reactions. However, the research like I disclosed earlier over the last few decades have really implicated mast cells in several other conditions because they regulate things like vascular vessel development

[00:04:04] and tissue homeostasis, which is a fancy way of saying my tissues are being balanced and in balance with the immune system, and other pathological conditions like gastrointestinal disorders and cardiovascular disease. So mast cells are distributed throughout the body and especially in the skeletal system, mast cells are involved in bone metabolite and bone disorders.

[00:04:27] Because mast cells store and make a bunch of inflammatory mediators, things like cytokines and enzymes which have been shown to regulate bone balance and bone homeostasis, they are also involved in those pathogenic skeletal diseases. Increasing numbers of mast cells have been found in patients who have reduced bone loss which is observed in conditions like post-menopausal osteoporosis and mastocytosis, which is a mast cell disorder.

[00:05:00] Increased number of mast cells have also been found in patients that have menopause-related bone loss as well, where histamine and other inflammatory conditions are effected. So the synovial fluid, which is a fluid around your bones and joints have been found to contain very large amounts of mast cells,

[00:05:21] particularly if people have osteoarthritis. These elevated concentrations of mast cells signal, along with other messengers like histamine and tryptase, allergy responses. So the inflammatory cytokines, the histamines and tryptases are part of the mechanism in which the mast cell mediates and controls your immune system.

[00:05:43] But those same messengers can affect the bones themselves. So mast cells are also tissue specific. So they produce messengers depending on where they’re at in the body to induce particular activities, to help our immune system fight. Those messengers are things like I’ve mentioned before: histamine, heparin, cytokines, things like tumi necrosis factor alpha, Interleukin-6,

[00:06:09] enzymes like tryptase, and growth factors like the vascular endothelial growth factor. So mast cells are not really found in the circulation. They’re more so distributed to the actual tissues in which they act. They are released specifically from the bone marrow. So mast cells are part of bone marrow formation, and they start out as immature cells and then they get matured as they’re sent to a particular tissue for action.

[00:06:38] So while mast cells are located at almost all tissues, high numbers are found in the tissues that face your external environment. So we find a lot of mast cells in the skin, in the lungs, and in the intestines where passage and exposure is high and very likely. Mast cells serve as a immune sort of sentinel, or an immune “cop”, to make sure that it can be the first line of defense against

[00:07:06] incoming pathogens…and mast cells last a long time, so they survive for a long period of time. Mast cells also react to the environment depending on the tissue they’re in and whether there’s damage or not. So mast cells receive information from things circulating in your bloodstream, pathogens and things like that.

[00:07:26] And then they also respond to tissue damage. So mast cells can also be activated by other immune cells: things like immunoglobulins, other cytokines, neuropeptides proteins called compliment proteins and things called Pampa, which are pathogen associated, molecular patterns. All of those are mechanisms in which the body

[00:07:49] starts to launch an inflammatory response. So activation of mast cells results in their release of preformed and newly synthesized or newly made mediators things like histamine. And often that happens through the process called de granulation do granulation is literally imagined the mast cell pops open and all of the ingredients pop out of the cell like histamine, but.

[00:08:15] They don’t always pop open and just drop all of their contents. They may signal with smaller amounts out to the different tissues because mast cells are present at tissue borders, especially things that. Receive a lot of exposure to pathogens. They are the first cells that actually respond to  invading pathogens.

[00:08:35] Mast cells can also be directed to pathogens and other byproducts made by things like bacteria and other organisms that survive in our body. mast cells can directly kill pathogens. They also enhance mucus production and in our different linings of her body, like the nasal passages, lungs, and intestines meant to immobilize pathogens and they actual modulate [00:09:00] your vascular permeability, your blood flow and they help initiate rapid immune response and rapid immune recruitment of other cells. So your body can actually fight off infection.

[00:09:12] So, mast cells are extremely important to initiating the immune response, but they’re also critical for immune healing. They are present in the connective tissue.

[00:09:22] So things like collagen ligaments, attendance, and the skin, and they can be activated by injury trauma. Radiation or even chemical agents. So it, mast cells are vital to our immune system response, but they can also play a role in the physiological activity of bone turnover. So mast cells are located mostly in the long part of the bone where bone remodeling mainly occurs not right up at the ends or the ends of the bones.

[00:09:51] They are preferentially located adjacent to the bone surfaces ongoing. Both grown bone growth and bone mediation. So [00:10:00] wherever there’s a lot of stimulation to the bone to grow is where they’re going to be mediated. Ma mast cells also were able to induce or modulator osteoclast activity by promoting the creation of osteoclasts with histamines and TNF alpha and interleukin six, which are inflammatory messengers and making inhibit osteoblasts by making messengers like TNF, alpha and interleukin.

[00:10:28] By contrast other mediators could act an osteo protective manner by stimulating osteoblasts by using things like transforming growth factor B, and they can also maybe reduce osteopathic class activity and. Building through the activity of interleukin 12 many of the research studies have shown that there’s this back and forth activity between the mast cell messengers and whether it’s increasing or decreasing bone loss.

[00:10:57] And what it shows is that it depends [00:11:00] on what’s really happening. So in 1983, a researcher Fallon and his colleagues reported an increase in numbers of mast cells in the iliac crest, in biopsies of females with post-menopausal osteoporosis compared to non osteoporotic males and females. So they saw an increased number of mast cells in women who were post-menopausal that indicated that the mast cells may have an action in bone.

[00:11:28] Confirming this many other authors actually observed the same thing that mast cells accumulated in the osteoporotic patients compared to healthy controls. Interesting Lee, the treatment of post-menopausal females with calcium. So they gave a supplemental calcium and a blocker of a histamine, one receptor, which are common drugs that are used for allergens and even digestive tract.

[00:11:53] Significantly increase the bone mineral density compared to calcium treatment alone. So they [00:12:00] found that the action of adjusting the histamine response actually improved the bone density in those post-menopausal women. This indicates that histamine one of the main preformed components as mast cells could be involved in osteoporosis, bone loss.

[00:12:17] Now we haven’t done a lot of human studies, but mouse studies revealed that estrogen strongly influences and affects mast cells and the release of those things like histamine. So when estrogen is absent, osteoclast formation was induced, it was made greater suggesting that estrogen may have an inhibitory effect on the osteoclast inducing potential of mast cells.

[00:12:41] Estrogen receptors expressed in the mast cells of various tissues and several tissues over the body. Show that estrogen influence mast cell migration breakdown and degranulation, where they drop their components and the release of those inflammatory [00:13:00] cytokines. So ultimately, what does that mean to somebody who are really working on trying to build their bone density?

[00:13:07]When we look at it, the observed effects of estrogen on mast cells are not always considered. Some authors found that estrogen induced mast cells and induced more bone loss and inhibitory effects on the mediator release. Therefore, the effects of estrogen on the mast cells depend on which tissue is being investigated.

[00:13:28] So when we have estrogen in the effect of mast cells on bone density, and those things are all present. Estrogen has a protective effect on the bones, but with the loss of estrogen mast cell activity, increasing histamine are going to have a greater effect on bone loss. So mast cells also appear to be related to bone loss.

[00:13:53] That is secondary to osteoporosis related to loss of estrogen and especially things like malnutrition or immobilization, because we know the biggest risk we’ve got with a fracture risk is immobilization and also malnourishment. And the body’s inability to basically recover from that injury. So mast cells that produce histamine and inflammatory cytokines may accelerate some of this activity.

[00:14:23] Because it actually may increase osteoclastic formation. So histamines, a mast cell component are, may play that crucial role in mast cell mediated osteoclast activity. Some researchers also show that histamine may support osteoclast formation. But it may not affect as much of the reabsorption activity.

[00:14:46] So what that really means is this indicates that histamine and mast cells may not be the only mechanism and osteoclast activation and that mast cell osteoclasts interaction might be more [00:15:00] complex. So what does that mean to you? So what it means to you is we know that estrogen has a protective effect on bone, particularly in women, as we’re still cycling.

[00:15:11] And if we’re women, post-menopausally, to have that additional supportive estrogen protects the bone and that estrogen turns down and dampens the effect of mast cells, which were part of our immune and inflammatory response, where they accelerate some of the bone loss. If I have other inflammatory activities that may be amplifying my mast cell activity, I may have mast cell activation syndrome.

[00:15:39] Or other immune stimulation symptoms and issues that increase my histamine activity that may in the absence of estrogen increase my likelihood for bone density issues and bone re remineralization problems. We need to do more research as a research community to understand the interaction between [00:16:00] mast cells, histamine and osteoporosis.

[00:16:02] But I think we can at least identify that excess of mast cell activity and histamine in a woman without circulating estrogen levels are going to probably play a role in bone loss and lack of bone mineralization. And I certainly hope that the research community continues to look at this going forward.

[00:16:23] Thank you very much for watching. I hope this was helpful for you. We’ll have much more video blogs coming to you soon about how you can really take on rebuilding your bone in osteoporosis and osteopenia. Thank you so much.

 


 

REFERENCES

Buckley MG, Walters C, Wong WM, Cawley MI, Ren S, Schwartz LB, et al. Mast cell activation in arthritis: detection of alpha- and beta-tryptase, histamine and eosinophil cationic protein in synovial fluid. Clin Sci. (1997) 93:363–70. doi: 10.1042/cs0930363

Schubert N, Dudeck J, Liu P, Karutz A, Speier S, Maurer M, et al. Mast cell promotion of T cell-driven antigen-induced arthritis despite being dispensable for antibody-induced arthritis in which T cells are bypassed. Arthritis Rheumatol. (2015) 67:903–13. doi: 10.1002/art.38996

Kroner J, Kovtun A, Kemmler J, Messmann JJ, Strauss G, Seitz S, et al. Mast cells are critical regulators of bone fracture-induced inflammation and osteoclast formation and activity. J Bone Miner Res. (2017) 32:2431–44. doi: 10.1002/jbmr.3234

Gurish MF, Austen KF. Developmental origin and functional specialization of mast cell subsets. Immunity. (2012) 37:25–33. doi: 10.1016/j.immuni.2012.07.003

Okayama Y, Kawakami T. Development, migration, and survival of mast cells. Immunol Res. (2006) 34:97–115. doi: 10.1385/IR:34:2:97

Urist MR,McLean FC. Accumulation of mast cells in endosteum of bones of calcium-deficient rats. AMA Arch Pathol. (1957) 63:239–51.

Taniguchi H. Mast cells in fracture healing: an experimental study using rat model. Nihon Seikeigeka Gakkai Zasshi. (1990) 64:949–57.

Turner RT, Iwaniec UT, Marley K, Sibonga JD. The role of mast cells in parathyroid bone disease. J Bone Miner Res. (2010) 25:1637–49. doi: 10.1002/jbmr.49

Biosse-Duplan M, Baroukh B, Dy M, de Vernejoul MC, Saffar JL. Histamine promotes osteoclastogenesis through the differential expression of histamine receptors on osteoclasts and osteoblasts. Am J Pathol. (2009) 174:1426–34. doi: 10.2353/ajpath.2009.080871

Ragipoglu, D., Dudeck, A., Haffner-Luntzer, M., Voss, M., Kroner, J., Ignatius, A., & Fischer, V. (2020). The Role of Mast Cells in Bone Metabolism and Bone Disorders. Frontiers in Immunology, 11, 163. https://doi.org/10.3389/fimmu.2020.00163

 

IMAGE CREDITS

Copyright: <a href=’https://www.123rf.com/profile_designua’>designua</a>

Copyright: <a href=’https://www.123rf.com/profile_rob3000′>rob3000</a> https://doi.org/10.3389/fimmu.2020.00163

 

Resources Mentioned

—>Claim your FREE 7-Day Osteoporosis Kickstart here! (the exact information you need to accelerate your path to stronger bones now)

Show notes and resources mentioned: www.bonecoach.com/osteoporosis-mast-cell-histamine

 

Watch The FREE Stronger Bones Masterclass
Watch The FREE Stronger Bones Masterclass
Watch Now

Apply to work with our team
Apply to work with our team
Apply Now

Medical Disclaimer

The information shared above is for informational purposes only and is not intended to provide medical or nutrition therapy advice; it does not diagnose, treat or cure any disease, condition; it is not to be used as a replacement or substitute for medical advice provided by physicians and trained medical professionals. If you are under the care of a healthcare professional or are currently using prescription medications, you should discuss any dietary and lifestyle changes or potential dietary supplements use with your doctor. You should not discontinue any prescription medications without first consulting your doctor.