Osteogenic Differentiation of Periosteal Cells During Fracture Healing

Abstract

Five to ten percent of fractures fail to heal normally leading to additional surgery, morbidity, and altered quality of life. Fracture healing involves the coordinated action of stem cells primarily coming from the periosteum which differentiate into the chondrocytes and osteoblasts, forming first the soft (cartilage) callus followed by the hard (bone) callus. These stem cells are accompanied by a vascular invasion that appears critical for the differentiation process and which may enable the entry of osteoclasts necessary for the remodeling of the callus into mature bone. However, more research is needed to clarify the signaling events that activate the osteochondroprogenitor cells of periosteum and stimulate their differentiation into chondrocytes and osteoblasts. Ultimately a thorough understanding of the mechanisms for differential regulation of these osteochondroprogenitors will aid in the treatment of bone healing and the prevention of delayed union and nonunion of fractures. In this review, evidence supporting the concept that the periosteal cells are the major cell sources of skeletal progenitors for the fracture callus will be discussed. The osteogenic differentiation of periosteal cells manipulated by Wnt/b-catenin, TGF/BMP, Ihh/PTHrP, and IGF-1/PI3K–Akt signaling in fracture repair will be examined. The effect of physical (hypoxia and hyperoxia) and chemical factors (reactive oxygen species) as well as the potential coordinated regulatory mechanisms in the periosteal progenitor cells promoting osteogenic differentiation will also be discussed. Understanding the regulation of periosteal osteochondroprogenitors during fracture healing could provide insight into possible therapeutic targets and thereby help to enhance future fracture healing and bone tissue engineering approaches.

Nano-copper-bearing stainless steel promotes fracture healing by accelerating the callus evolution process

“…As is known, osteoclasts are necessary for the remodeling of callus into mature bone. 47,48 Although the effect of 317L-Cu SS on the functions of osteoclasts is not clear, Cu 2+ seems to have some effect on osteoclasts, which still needs further study. Li and Yu found that extracellular Cu 2+ could inhibit osteoclastic resorption on dental slices.…”

Evaluation of bone marrow microenvironment could change how myelodysplastic syndromes are diagnosed and treated

“…This has been observed during fracture healing, which requires coordinated action of stem cells that come primarily from the periosteal region and that are able to differentiate into chondrocytes and osteoblasts to form the fibrocartilage callus (10). Post-embryonically, one of the most important sources of MSCs is the periosteum.…”

“…Higher Ang-1 expression in BM has been shown to be poor prognostic factor irrespective of age, karyotype and IPPS score in MDS settings (96). With the progression of the disease toward overt leukemia it was observed a decrease of BM angiogenesis and a switch of the production of cytokines toward anti-angiogenic profile (i.e., secretion of TGF-β) (10).…”

Acidic pH environment induces autophagy in osteoblasts

“…Bone fracture healing is a complex process, initially the soft (cartilage) callus forms, followed by formation of the hard (bone) callus. Although most fractures heal routinely, about 5–10% of fractures fail to heal normally and are described as displaying bone nonunion3. Many factors contribute to the pathogenesis of a delayed union or bone nonunion.…”

“…Many factors contribute to the pathogenesis of a delayed union or bone nonunion. It is known that osteoblasts (OBs), the cells responsible for bone formation, play a significant role3. The extreme adverse microenvironment in fracture sites has a negative effect on the survival of OBs, which may be a key cause for bone nonunion and segmental bone loss after fractures.…”