Astrocytes are the most populous glial cells in the central nervous system (CNS). They are essential to CNS physiology and play important roles in the maintenance of homeostasis, development of synaptic plasticity, and neuroprotection. Nevertheless, under the influence of certain factors, astrocytes may also exert detrimental effects through a process of reactive astrogliosis. Previous studies have shown that astrocytes have more than one type of polarization. Two types have been extensively researched. One is a damaging change that occurs under inflammation and has been termed A1 astrocyte, while the other is a restorative change that occurs under ischemic induction and was termed A2 astrocyte. Researchers are now increasingly paying attention to the role of astrocytes in spinal cord injury (SCI), degenerative diseases, chronic pain, neurological tumors, and other CNS disorders. In this review, we discuss (a) the characteristics of polarized astrocytes, (b) the relationship between astrocyte polarization and SCI, and (c) new implications of reactive astrogliosis for future SCI therapies.

Long noncoding RNAs (LncRNAs) have been implicated in the regulation of adipocyte and osteoblast differentiation. However, the functional contributions of LncRNAs to adipocyte or osteoblast differentiation remain largely unexplored. In the current study we have identified a novel LncRNA named peroxisome proliferator-activated receptor γ coactivator-1β-OT1 (PGC1β-OT1). The expression levels of PGC1β-OT1 were altered during adipogenic and osteogenic differentiation from progenitor cells. 5′-and 3′-rapid amplification of cDNA ends (RACE) revealed that PGC1β-OT1 is 1759 nt in full length. Overexpression of PGC1β-OT1 in progenitor cells inhibited adipogenic differentiation, whereas silencing of endogenous PGC1β-OT1 induced adipogenic differentiation. By contrast, overexpression of PGC1β-OT1 in progenitor cells stimulated, whereas silencing of PGC1β-OT1 inhibited osteogenic differentiation. In vivo experiment showed that silencing of endogenous PGC1β-OT1 in marrow stimulated fat accumulation and decreased osteoblast differentiation in mice. Mechanism investigations revealed that PGC1β-OT1 contains a functional miR-148a-3p binding site. Overexpression of the mutant PGC1β-OT1 with mutation at the binding site failed to regulate either adipogenic or osteogenic differentiation. In vivo crosslinking combined with affinity purification studies demonstrated that PGC1β-OT1 physically associated with miR-148a-3p through the functional miR-148a-3p binding site. Furthermore, PGC1β-OT1 affected the expression of endogenous miR-148a-3p and its target gene lysine-specific demethylase 6b (KDM6B). Supplementation of miR-148a-3p in progenitor cells blocked the inhibitory effect of PGC1β-OT1 on adipocyte formation. Moreover, overexpression of Kdm6b restored the osteoblast differentiation which was inhibited by silencing of endogenous PGC1β-OT. Our studies provide evidences that the novel LncRNA PGC1β-OT1 reciprocally regulates adipogenic and osteogenic differentiation through antagonizing miR-148a-3p and enhancing KDM6B effect.

No abstract

No abstract

No abstract

No abstract

No abstract

Recent evidence revealed that lysophosphatidic acid receptor 4 (LPAR4) plays a role in osteogenesis and bone remodeling in mice. However, the molecular mechanism by which LPAR4 controls osteogenic and adipogenic differentiation of mesenchymal progenitor cells remains pending. In the current study, our data showed that Lpar4 was expressed in bone and adipose tissue and the expression increased during osteoblast and adipocyte differentiation. Lpar4 overexpression in stromal ST2 and preosteoblastic MC3T3‐E1 cells inhibited osteogenic differentiation. By contrast, Lpar4 overexpression in ST2 and mesenchymal C3H10T1/2 cells enhanced adipogenic differentiation. Conversely, depletion of endogenous Lpar4 in the progenitor cells induced osteogenic differentiation and inhibited adipogenic differentiation. Furthermore, enhanced osteoblast differentiation and alleviated fat accumulation were observed in marrow of mice after in vivo transfection of Lpar4 siRNA. Mechanism investigations revealed that LPAR4 inhibited the activation of ras homolog family member A (RhoA)/Rho‐associated kinases 1 (ROCK1) and canonical Wnt signal pathways. ROCK1 was shown to be able to activate Wnt/β‐catenin pathway. We further demonstrated that the overexpression of ROCK1 stimulated osteogenic differentiation and restrained adipogenic differentiation from stromal progenitor cells. Moreover, overexpression of ROCK1 attenuated the inhibition of osteogenic differentiation by LPAR4. The current study has provided evidences demonstrating that RhoA/ROCK1 activates β‐catenin signaling to promote osteogenic differentiation and conversely restrain adipogenic differentiation. The inactivation of RhoA/ROCK1/β‐catenin signaling is involved in LPAR4 regulation of the directional differentiation of marrow stromal progenitor cells.