Osteogenic differentiation: a universal cell program of heterogeneous mesenchymal cells or a similar extracellular matrix mineralizing phenotype?

Abstract

Despite the popularity of mesenchymal stem cells (MSCs), many fundamental aspects of their physiology still have not been understood. The information accumulated to date argues that MSCs from different sources vary in their differentiation potential and, probably, in molecular mechanisms of trilineage differentiation. Therefore, this review consists of two parts. Firstly, we focus on the data on inter- and intra-source variation of MSCs. We discuss in detail MSC variation at the single-cell level and direct omics comparison of MSCs from four main tissue sources: bone marrow, adipose tissue, umbilical cord and tooth. MSCs from all tissues represent heterogeneous populations in vivo with sub-populational structures reflecting their functional role in the tissue. After in vitro cultivation MSCs lose their natural heterogeneity, but obtain a new one, which might be regarded as a cultivation artifact. Nevertheless, MSCs from various sources still keep their functional differences after in vitro cultivation. In the second part of the review, we discuss how these differences influence molecular mechanisms of osteogenic differentiation. We highlight at least one subtype of mesenchymal cells differentiation with matrix mineralization — odontoblastic differentiation. We also discuss differences in molecular mechanisms of pathological heterotopic osteogenic differentiation of valve interstitial and tumor cells, but these assumptions need additional empirical confirmation. Finally, we observe differences in osteogenic differentiation molecular mechanisms of several MSC types and argue that this differentiation might be influenced by the cell context. Nevertheless, bone marrow and adipose MSCs seem to undergo osteogenic differentiation similarly, by the same mechanisms.

Isolation of Human Osteoblast Cells Capable for Mineralization and Synthetizing Bone-Related Proteins In Vitro from Adult Bone

“…The advantage of the cells, isolated by the described method compared to bone marrow-derived osteoprogenitors, is that the resulting cell population is more homogenous. According to flow cytometry characteristics, there is no contamination of blood-derived cells in OB cultures and one does not need to use sorting after cell isolation, while for bone marrow-derived osteoblasts it is a necessary step [ 18 ]. This makes the described method cheaper and faster.…”

“…Neither osteopontin, nor periostin and osteocalcin null mice are lethal or display major bone abnormalities [ 16 ]. Type 1 collagen is a key marker of an early proliferation and synthetic phase of osteogenic differentiation [ 18 ]. The requirement of collagen, osteopontin, and periostin at the stage of mineralization may be decreased.…”

“…Moreover, it is known that the mechanisms of osteogenic differentiation vary between species and a response of osteoblasts of non-human origin to pharmacological agents may differ from that of human osteoblasts. In our recent review, we discussed that many alterations are described for the expression of transcription factor RUNX2 in response to osteogenic stimuli and thus the expression of RUNX2 might be cell type/model-dependent [ 18 ]. For example, dexamethasone stimulated RUNX2 production in human osteoblast cell lines, but inhibited RUNX2 in rodent osteoblasts [ 18 , 29 ].…”

“…In our recent review, we discussed that many alterations are described for the expression of transcription factor RUNX2 in response to osteogenic stimuli and thus the expression of RUNX2 might be cell type/model-dependent [ 18 ]. For example, dexamethasone stimulated RUNX2 production in human osteoblast cell lines, but inhibited RUNX2 in rodent osteoblasts [ 18 , 29 ]. That is the reason to test antiosteoporosis drugs and materials for bone prosthesis using human osteoblasts of bone origin in preclinical studies in addition to animal models.…”

Similar, but not the same: multi-omics comparison of human valve interstitial cells and osteoblast osteogenic differentiation expanded with an estimation of data-dependent and data-independent PASEF

“…Although it is generally assumed that osteogenic differentiation of VICs is similar to that of osteoblasts, there is still no empirical confirmation of this assumption because of the lack of multi-omics studies that describe the molecular mechanisms of adult osteoblast differentiation and physiology. 9 Therefore, we aimed to perform the multi-omics comparison of molecular mechanisms of VICs and osteoblast osteogenic differentiation in vitro .…”