Skeletal Stem Cells: Origins, Functions, and Uncertainties

Abstract

The development and maintenance of the skeleton requires a steady source of skeletal progenitors to provide the osteoblasts and chondrocytes necessary for bone and cartilage growth and development. The current model for skeletal stem cells (SSCs) posits that SSC/progenitor cells are present in bone marrow (BM) and other osteogenic sites such as cranial sutures where they undergo self-renewal and differentiation to give rise to the main skeletal tissues. SSCs hold great promise for understanding skeletal biology and genetic diseases of bone as well as for the advancement of bone tissue engineering and regenerative medicine strategies. In the past few years, a considerable effort has been devoted to identifying and purifying skeletal stem cells and determining their contribution to bone formation and homeostasis. Here, we review recent progress in this area with particular emphasis on the discovery of specific SSC markers, their use in tracking the progression of cell populations along specific lineages and the regulation of SSCs in both the appendicular and cranial skeleton.

Bone marrow adipose cells – cellular interactions and changes with obesity

“…The adipogenic-lineage-committed cells were shown to differentiate to pre-adipocytes, which are negative for CD45, CD31 and Sca1, but positive for zinc finger protein 423 (zfp423) (Ambrosi et al, 2017). Furthermore, several other markers such as osterix (Osx), leptin receptor (LepR), nestin (Nes) and Gremlin1 (Grem1) have also proven reliable to classify bone marrow MSCs (Mohamed et al, 2017).…”

New Insights on Properties and Spatial Distributions of Skeletal Stem Cells

“…Mesenchymal cells in hematopoietic niche often provide regulatory cues for HSC development and homeostasis. At the same time, many important discoveries of SSCs are based on vasculature, indicating a function of the vascular microenvironment for SSCs [26, 63–65]. The association between MSCs/SSCs and hematopoiesis is the focus of the study [66].…”

“…Furthermore, serial transplantation of isolated SSCs from the primary donor results in de novo formation of heterotopic ossicles. In comparison, MSCs barely exhibit aforementioned potential [17, 18, 24–26].…”

Marrow Adipose Tissue: Its Origin, Function, and Regulation in Bone Remodeling and Regeneration

“…So the second question raised is do progenitors residing in the bone marrow give rise to marrow adipocytes. Recent studies successfully identified several markers for SSCs, including osterix (Osx) , leptin receptor (LepR) , nestin (Nes) , and Gremlin1 (Grem1) [ 39 ]. Osterix is a transcription factor crucial for osteoblast differentiation and marks different precursors at the fetal, perinatal, and adult bone stage in Osx- CreERT mice [ 40 , 41 ].…”