Myeloid‐derived growth factor (MYDGF) protects bone mass through inhibiting osteoclastogenesis and promoting osteoblast differentiation

Abstract

Whether bone marrow regulates bone metabolism through endocrine and paracrine mechanism remains largely unknown. Here, we found that (i) myeloid cell-specific myeloid-derived growth factor (MYDGF) deficiency decreased bone mass and bone strength in young and aged mice; (ii) myeloid cell-specific MYDGF restoration prevented decreases in bone mass and bone strength in MYDGF knockout mice; moreover, myeloid cell-derived MYDGF improved the progress of bone defects healing, prevented ovariectomy (OVX)-induced bone loss and age-related osteoporosis; (iii) MYDGF inhibited osteoclastogenesis and promoted osteoblast differentiation in vivo and in vitro; and (iv) PKCβ-NF-κB and MAPK1/ 3-STAT3 pathways were involved in the regulation of MYDGF on bone metabolism. Thus, we concluded that myeloid cell-derived MYDGF is a positive regulator of bone homeostasis by inhibiting bone resorption and promoting bone formation. MYDGF may become a potential novel therapeutic drug for osteoporosis, and bone marrow may become a potential therapeutic target for bone metabolic disorders.

Stat3 Signaling Pathway: A Future Therapeutic Target for Bone-Related Diseases

“…On the other side of the disorder of osteohomeostasis, the engagement of Stat3 in osteoblast bone formation is likewise crucial. First, Stat3 upregulates Runx2 transcriptional activity, induces alkaline phosphatase (ALP) activation and calcium nodule mineralization by binding to the osteogenesis-associated transcription factor Runx2 ( Xu et al, 2022 ). The subsequent ChIP experiments reveal that Stat3 directly binds to the promoter of the late osteogenic marker osteocalcin (OCN) and further enhances this effect upon the incorporation of Runx2 ( Xu et al, 2020 ).…”

“…Elevated leptin in serum induces activation of Stat3 in cartilage and leads to pathological activation of CD14/TLR4, which further provokes obesity-associated inflammation and MMP-13 expression ( Jiang et al, 2021 ). Analogously, the myeloid-derived growth factor (MYDGF) increases Stat3 phosphorylation on S727 ( Xu et al, 2022 ). MYDGF promotes bone defect healing by promoting ALP activity and mineralization in primary cranial osteoblasts, in which Stat3 activation plays a pivotal role ( Xu et al, 2022 ).…”

“…Analogously, the myeloid-derived growth factor (MYDGF) increases Stat3 phosphorylation on S727 ( Xu et al, 2022 ). MYDGF promotes bone defect healing by promoting ALP activity and mineralization in primary cranial osteoblasts, in which Stat3 activation plays a pivotal role ( Xu et al, 2022 ). Nevertheless, the road from targeting Stat3 to mature therapies for bone-related diseases remains long, and therapeutic applications for either activating or inhibiting Stat3 have limitations.…”

Anti-osteoporosis treatments changed body composition in postmenopausal women: A systematic review and meta-analysis

“…For FM, the meta-analysis on HRT presented a positive effect in reducing FM, which is also consistent with our previous findings that ovariectomy-induced bone loss in mice tends to display a markedly increased body weight. [35] Of note, the meta-analysis still showed substantial heterogeneity ( I 2 = 67.0%, Q = 30.34). Therefore, we conducted the subgroup analyses on study region, age, duration of follow-up, and study type to find out the possible explanations.…”

The Role of Growth Factors in the Repair of Motor Injury

“…A Liedert et al found that The growth factor midkine (Mdk) plays a key role in bone remodeling, and it is expressed in the processes of bone formation and fracture repair ( Liedert et al, 2014 ). A recent in vivo animal study reported that myelogenous growth factor (MYDGF) protects bone mass by inhibiting osteoclastogenesis and promoting osteoblast differentiation, and is a positive modulator of bone homeostasis ( Xu et al, 2022 ). Similarly, growth factors play an important role in the repair of joint injuries.…”