A soluble activin type IIA receptor mitigates the loss of femoral neck bone strength and cancellous bone mass in a mouse model of disuse osteopenia

Bone Geometry Is Altered by Follistatin‐Induced Muscle Growth in Young Adult Male Mice

“…(23) These mice exhibit high bone mass and strength, (17,(24)(25)(26)(27) and changes in bone shape, including at sites of muscle attachment. (24,28) Systemic TGF-β/activin inhibition with soluble decoy receptors (ACVR2A-Fc (29)(30)(31) or ACVR2B-Fc (29,(32)(33)(34) ) not only increased muscle mass but increased trabecular bone volume in mice and monkeys, and further increased trabecular bone volume in Mstn-null mice. (32) While the changes to bone shape, size and mass were likely influenced by the muscle hypertrophy, there is increasing evidence for direct actions of activin ligands on both osteoblasts and osteoclasts.…”

Inhibition of the activin receptor signaling pathway: A novel intervention against osteosarcoma

“…Activin A and growth differentiation factor 11 (GDF11) are members of the TGFβ superfamily that have recently been proposed as negative regulators of bone mass 3–5 . Their neutralization have been reported to increase bone mass, bone strength, or bone formation markers in postmenopausal women or preclinical models of bone loss 5–8 . In addition, aberrant activin A signaling has been shown to invoke local and systemic inflammation and to be a driving factor in various cancers 9,10 …”

“…Activin A and GDF11 initiate signaling via membrane proteins known as activin type II receptors (ActRIIs; ActRIIA and ActRIIB). Collectively, compounds that prevent transduction through these receptors may be referred to as inhibitors of the activin receptor signaling pathway (IASPs) 6,16 …”

“…[3][4][5] Their neutralization have been reported to increase bone mass, bone strength, or bone formation markers in postmenopausal women or preclinical models of bone loss. [5][6][7][8] In addition, aberrant activin A signaling has been shown to invoke local and systemic inflammation and to be a driving factor in various cancers. 9,10 In osteosarcoma, pathological bone remodeling is thought to maintain a "vicious cycle" that nourishes tumor cells by release of growth factors stored within the bone matrix.…”

“…Collectively, compounds that prevent transduction through these receptors may be referred to as inhibitors of the activin receptor signaling pathway (IASPs). 6,16 Bisphosphonates are chemically stable derivatives of inorganic pyrophosphate that have a natural predilection for hydroxyapatite crystals. 17 During bone remodeling, bisphosphonate is absorbed by the osteoclast and incorporated into the cell's adenosine triphosphate production.…”