A bone-specific adipogenesis pathway in fat-free mice defines key origins and adaptations of bone marrow adipocytes with age and disease

Zhang, Xiao; Robles, Hero; Magee, Kristann; Lorenz, Madelyn R.; Wang, Zhaohua; Harris, Charles; Craft, Clarissa S.; Scheller, Erica L.

doi:10.7554/elife.66275

Cited by 32 publications

(22 citation statements)

References 44 publications

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“…Adipoq-Cre recombination in the mouse skeleton occurs in marrow adipocytes, in a network of stromal cells residing among hematopoietic cells and around blood vessels, and in cells lining the trabecular bone surfaces. 11 , 13 – 15 Adq -marrow stromal cells were reported to coincide with a fraction of Lepr-Cre- targeted stromal cells 13 and to largely overlap with the PDGFRβ + /VCAM-1 + /CXCL12 + (CAR) stromal cell subsets. 14 In addition, it was shown that the majority of Adq -marrow stromal/perivascular cells are post-natal adipocyte progenitors, named MALPs, that support marrow vasculature and are involved in the regulation of bone resorption.…”

Section: Discussionmentioning

confidence: 99%

GsαR201C and estrogen reveal different subsets of bone marrow adiponectin expressing osteogenic cells

et al. 2022

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The Gsα/cAMP signaling pathway mediates the effect of a variety of hormones and factors that regulate the homeostasis of the post-natal skeleton. Hence, the dysregulated activity of Gsα due to gain-of-function mutations (R201C/R201H) results in severe architectural and functional derangements of the entire bone/bone marrow organ. While the consequences of gain-of-function mutations of Gsα have been extensively investigated in osteoblasts and in bone marrow osteoprogenitor cells at various differentiation stages, their effect in adipogenically-committed bone marrow stromal cells has remained unaddressed. We generated a mouse model with expression of GsαR201C driven by the Adiponectin (Adq) promoter. Adq-GsαR201C mice developed a complex combination of metaphyseal, diaphyseal and cortical bone changes. In the metaphysis, GsαR201C caused an early phase of bone resorption followed by bone deposition. Metaphyseal bone formation was sustained by cells that were traced by Adq-Cre and eventually resulted in a high trabecular bone mass phenotype. In the diaphysis, GsαR201C, in combination with estrogen, triggered the osteogenic activity of Adq-Cre-targeted perivascular bone marrow stromal cells leading to intramedullary bone formation. Finally, consistent with the previously unnoticed presence of Adq-Cre-marked pericytes in intraosseous blood vessels, GsαR201C caused the development of a lytic phenotype that affected both cortical (increased porosity) and trabecular (tunneling resorption) bone. These results provide the first evidence that the Adq-cell network in the skeleton not only regulates bone resorption but also contributes to bone formation, and that the Gsα/cAMP pathway is a major modulator of both functions.

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Section: Discussionmentioning

confidence: 99%

GsαR201C and estrogen reveal different subsets of bone marrow adiponectin expressing osteogenic cells

et al. 2022

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“…(C) Adiponectinprogenitors are predominantly of the osteogenic lineage, but are also able to differentiate into BMAs in metabolic disorders or in aging adults. This population elicits similar properties as cBMAs (30). BMSC, bone mesenchymal stem cells; rBMA, regulated bone marrow adipocyte; cBMA, constitutive bone marrow adipocyte; MALP, marrow adipogenic lineage precursor; C/EBP, CCAAT/enhancer-binding protein; FA, fatty acid; PPARg, peroxisome proliferator-activated receptor gamma.…”

Section: Originmentioning

confidence: 99%

“…This population was able to differentiate into ectopic BMAs with age and metabolic diseases. These BMAs have increased lipid storage and are not thermogenic as they are unresponsive to cold stress or β3-adrenergic stimulation ( 30 ). Despite that adiponectin is an essential adipocyte specific cytokine, the discovery of adiponectin-independent BMA subsets allows to speculate that further origins of BMAs remain to be revealed.…”

Section: Originmentioning

confidence: 99%

“…(B) MALPs are a newly defined primarily adipogenic sub-population that arises from adiponectin + progenitors. Factors like acute injury and aging can trigger osteogenic differentiation of MALPs ( 30 , 31 ). (C) Adiponectin - progenitors are predominantly of the osteogenic lineage, but are also able to differentiate into BMAs in metabolic disorders or in aging adults.…”

Section: Originmentioning

confidence: 99%

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Distinct Metabolism of Bone Marrow Adipocytes and their Role in Bone Metastasis

Cao

Gaculenko

et al. 2022

Front. Endocrinol.

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Bone marrow adipocytes (BMAs) represent 10% of the total fat mass of the human body and serve as an energy reservoir for the skeletal niche. They function as an endocrine organ by actively secreting fatty acids, cytokines, and adipokines. The volume of BMAs increases along with age, osteoporosis and/or obesity. With the rapid development of multi-omic analysis and the advance in in vivo imaging technology, further distinct characteristics and functions of BMAs have been revealed. There is accumulating evidence that BMAs are metabolically, biologically and functionally unique from white, brown, beige and pink adipocytes. Bone metastatic disease is an uncurable complication in cancer patients, where primary cancer cells spread from their original site into the bone marrow. Recent publications have highlighted those BMAs could also serve as a rich lipid source of fatty acids that can be utilized by the cancer cells during bone metastasis, particularly for breast, prostate, lung, ovarian and pancreatic cancer as well as melanoma. In this review, we summarize the novel progressions in BMAs metabolism, especially with multi-omic analysis and in vivo imaging technology. We also update the metabolic role of BMAs in bone metastasis, and their potential new avenues for diagnosis and therapies against metastatic cancers.

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“…Therefore, TCM uses both interior therapies in conjunction to external therapy. TCM considers 3 phases when it comes to bone deformities: 1) during first phase, there is harm to the blood vessels due to stagnation of “qi” and blood, and also obstructed meninges, which together leads to pain; 2) in the second phase, the inflammation eventually subsides and the pain is significantly reduced, but the bruises remain, and connective tissues are not repaired; 3) in the third phase, the overall bone damage has now been healed, but remedy to pacify and improve bone regeneration, and improve the internal environment is yet required ( Tang et al, 2021 ; Zhang et al, 2021 ). Icariin (ICA) being a traditional Chinese medicine which was found to repair the vascular system and successfully modulate intracellular senescence in bones.…”

Section: Traditional Chinese Medicines In Osteoporosis and Bone Regen...mentioning

confidence: 99%

Role of Traditional Chinese Medicine in Bone Regeneration and Osteoporosis

Peng¹,

Xu²,

You³

2022

Front. Bioeng. Biotechnol.

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According to World Health Organization (WHO), osteoporosis is a systematic bone disability marked by reduced bone mass and microarchitectural degeneration of osseous cells, which leads to increased bones feebleness and fractures vulnerability. It is a polygenetic, physiological bone deformity that frequently leads to osteoporotic fractures and raises the risk of fractures in minimal trauma. Additionally, the molecular changes that cause osteoporosis are linked to decreased fracture repair and delayed bone regeneration. Bones have the ability to regenerate as part of the healing mechanism after an accident or trauma, including musculoskeletal growth and ongoing remodeling throughout adulthood. The principal treatment approaches for bone loss illnesses, such as osteoporosis, are hormone replacement therapy (HRT) and bisphosphonates. In this review, we searched literature regarding the Traditional Chinese medicines (TCM) in osteoporosis and bone regeneration. The literature results are summarized in this review for osteoporosis and bone regeneration. Traditional Chinese medicines (TCM) have grown in popularity as a result of its success in curing ailments while causing minimal adverse effects. Natural Chinese medicine has already been utilized to cure various types of orthopedic illnesses, notably osteoporosis, bone fractures and rheumatism with great success. TCM is a discipline of conventional remedy that encompasses herbal medication, massage (tui na), acupuncture, food, and exercise (qigong) therapy. It is based on more than 2,500 years of Chinese healthcare profession. This article serves as a comprehensive review summarizing the osteoporosis, bone regeneration and the traditional Chinese medicines used since ancient times for the management of osteoporosis and bone regeneration.

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A bone-specific adipogenesis pathway in fat-free mice defines key origins and adaptations of bone marrow adipocytes with age and disease

Cited by 32 publications

References 44 publications

GsαR201C and estrogen reveal different subsets of bone marrow adiponectin expressing osteogenic cells

GsαR201C and estrogen reveal different subsets of bone marrow adiponectin expressing osteogenic cells

Distinct Metabolism of Bone Marrow Adipocytes and their Role in Bone Metastasis

Role of Traditional Chinese Medicine in Bone Regeneration and Osteoporosis

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